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Preview: MedWorm: Hereditary Nonpolyposis Colorectal Cancer

MedWorm: Hereditary Nonpolyposis Colorectal Cancer



MedWorm.com provides a medical RSS filtering service. Over 7000 RSS medical sources are combined and output via different filters. This feed contains the latest news and research in the Hereditary Nonpolyposis Colorectal Cancer category.



Last Build Date: Sat, 26 Mar 2016 15:11:21 +0100

 



Upper tract urothelial carcinoma: epidemiology, high risk populations, and detection.

Fri, 25 Mar 2016 12:35:02 +0100

Authors: Redrow GP, Matin SF Abstract Upper tract urothelial carcinoma (UTUC) is a rare but highly morbid genitourinary malignancy. In 2014 approximately 15000 new cases were diagnosed in the United States. It accounts for approximately 5-10% of all urothelial cell carcinomas, and 10% of renal tumors. Recent research has increased understanding of the epidemiology of this disease, including several high-risk populations. Environmental exposure to tobacco as well as aristolochic acid, and other carcinogens significantly increase the development of UTUC. Additionally, the genetic condition of hereditary nonpolyposis colorectal carcinoma (HNPCC), also known as Lynch Syndrome (LS) is linked to development of UTUC. Advances in imaging, ureteroscopy, cytological techniques and pathologic...

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Hereditary non‐polyposis colorectal cancer/Lynch syndrome in three dimensions

Wed, 16 Mar 2016 00:00:00 +0100

ConclusionHereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance. (Source: ANZ Journal of Surgery)



Diagnosis and Management of Endometrial Cancer.

Tue, 15 Mar 2016 00:00:00 +0100

Authors: Braun MM, Overbeek-Wager EA, Grumbo RJ Abstract Endometrial cancer is the most common gynecologic malignancy. It is the fourth most common cancer in women in the United States after breast, lung, and colorectal cancers. Risk factors are related to excessive unopposed exposure of the endometrium to estrogen, including unopposed estrogen therapy, early menarche, late menopause, tamoxifen therapy, nulliparity, infertility or failure to ovulate, and polycystic ovary syndrome. Additional risk factors are increasing age, obesity, hypertension, diabetes mellitus, and hereditary nonpolyposis colorectal cancer. The most common presentation for endometrial cancer is postmenopausal bleeding. The American Cancer Society recommends that all women older than 65 years be informed of the ...



ReCAP: Oncologists Selection of Genetic and Molecular Testing in the Evolving Landscape of Stage II Colorectal Cancer [FOCUS ON QUALITY]

Wed, 09 Mar 2016 00:00:00 +0100

In this study, we asked: how does the family history of patients with stage II CRC influence medical oncologists’ selection of genetic and molecular testing, both related and unrelated to Lynch syndrome? SUMMARY ANSWER: We found that oncologists’ self-reported ordering of Lynch syndrome–related tests was strongly associated with the strength of CRC family history, but even so, not all oncologists would order germline testing for mismatch repair (MMR) genes, much less screen for Lynch syndrome by ordering microsatellite instability and/or immunohistochemistry for MMR proteins, in a patient scenario with the strongest family history of CRC (Table 2). We also found overtesting of KRAS and Oncotype DX for stage II CRC associated with certain practice and provider characteris...



Six Ways to Lower Your Risk for Colon Cancer

Mon, 07 Mar 2016 23:23:27 +0100

By Stacy Simon Colon cancer is one of the more common cancers in the US. About 1 in 20 Americans will develop colon cancer at some point during their lifetime. But there are things you can do to help lower your colon cancer risk. Here are 6 ways to help protect your colon health. Get screened for colon cancer. Screenings are tests that look for cancer before signs and symptoms develop. Colon screenings can often find growths called polyps that can be removed before they turn into cancer. These tests also can find colon cancer earlier, when treatments are more likely to be successful. The American Cancer Society recommends testing starting at age 50 for most people; talk to your doctor about when you should start and which tests might be right for you. RESOURCES: How the American Cance...



Hereditary non-BRCA gynaecological tumors.

Wed, 02 Mar 2016 16:12:02 +0100

Authors: Vellone VG, Paudice M, Varesco L Abstract Early diagnosis and proper management of gynecologic malignancies represent a challenge in modern oncology. A growing interest has arisen around the gynecological manifestations of hereditary cancer syndromes. In particular, the discovery of the BRCA1 and BRCA2 genes in ovarian cancer and the mismatch repair genes (MMR) in endometrial carcinoma has revolutionized our approach to the diagnosis and screening of women for ovarian and uterine cancers. The clinical, genetic and pathological features of hereditary cancer syndromes with gynecological manifestations are reviewed focusing on Lynch Syndrome, also known as Hereditary Nonpolyposis Colorectal Carcinoma (HNPCC), Peutz-Jeghers Syndrome, Cowden Syndrome or Multiple Hamartoma Syndr...

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Lichen Sclerosus in a Patient With a History of Hereditary Nonpolyposis Colorectal Cancer.

Tue, 01 Mar 2016 00:00:00 +0100

Authors: Florek AG, Cotliar J PMID: 26992266 [PubMed - in process] (Source: The American Journal of the Medical Sciences)



Signs and Symptoms of Colon Cancer

Mon, 29 Feb 2016 18:21:00 +0100

By Stacy Simon Many of the symptoms of colon cancer can also be caused by something that isn’t cancer, such as infection, hemorrhoids, irritable bowel syndrome, or inflammatory bowel disease. In most cases, people who have these symptoms do not have cancer. Still, if you have any of these problems, it is a sign that you should go to the doctor so the cause can be found and treated, if needed:A change in bowel habits, such as diarrhea, constipation, or narrowing of the stool, that lasts for more than a few daysA feeling that you need to have a bowel movement that is not relieved by doing soRectal bleedingDark stools, or blood in the stool (often, though, the stool will look normal)Cramping or abdominal (belly) painWeakness and fatigueUnintended weight lossWhen colon cancer does turn o...



Risk-reduction surgery in pediatric surgical oncology: A perspective

Thu, 18 Feb 2016 00:00:00 +0100

A small percentage of pediatric solid cancers arise as a result of clearly identified inherited predisposition syndromes and nongenetic lesions. Evidence supports preemptive surgery for children with genetic [multiple endocrine neoplasia type 2 (MEN2), familial adenomatous polyposis syndrome (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), and hereditary diffuse gastric cancer (HDGC) and nongenetic [thyroglossal duct cysts (TGDC), congenital pulmonary airway malformations (CPAM), alimentary tract duplication cysts (ATDC), and congenital choledochal cysts (CCC)] developmental anomalies. (Source: Journal of Pediatric Surgery)



Observational Study: Familial Relevance and Oncological Significance of Revised Bethesda Guidelines in Colorectal Patients That Have Undergone Curative Resection

Mon, 01 Feb 2016 06:00:00 +0100

Abstract: Amsterdam criteria for the hereditary nonpolyposis colorectal cancer (HNPCC) exclude most suspect cases of possible hereditary colorectal cancer (CRC). By contrast, revised Bethesda guidelines excessively broaden the disease spectrum. The aim of this study is to retrospectively evaluate the cliniciopathilogical characteristics of patients fulfilling the revised Bethesda guidelines and to review the efficacy and limitations of the revised guidelines. This retrospective study enrolled 3609 patients who underwent curative surgery for primary CRC. Patients were classified into the Bethesda group or the control group according to whether they fulfilled the revised Bethesda guidelines. Patients were further categorized when they fulfilled a minimum of 2 items of the revised guidelines...



The impact of hereditary colorectal cancer on the Indian population

Mon, 01 Feb 2016 00:00:00 +0100

Conclusion: The overall incidence of colorectal cancer is low in India. There is a tendency to affect a relatively younger age group, and we infer that the incidence of hereditary colorectal cancer is high and is similar to the Western countries. (Source: Indian Journal of Cancer)

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Targeted next‐generation sequencing of 22 mismatch repair genes identifies Lynch syndrome families

Mon, 25 Jan 2016 00:00:00 +0100

In conclusion, we have identified two LS families from the sporadic EC patients, one without a family history of cancer, supporting the notion for universal MMR screening of EC patients. In addition, we have detected three novel class 3 variants in EC cases. We have, in addition discovered a polygenic interaction which is the most likely cause of cancer development in a HNPCC patient that could explain previous inconsistent results reported on an intronic EXO1 variant. This study provides evidence that mutations in mismatch repair screening is highly relevant to endometrial cancer diagnostics and that polygenic interactions may be causative in hereditary nonpolyposis colorectal cancer. There is potential for rapid uptake of these testing strategies to the clinic through only small modific...



Lynch Syndrome or Hereditary Nonpolyposis...

Wed, 20 Jan 2016 00:00:00 +0100

Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) increases the risk of developing colon and other cancers. (Source: About.com Colon Cancer)



Development of certain new 2-substituted-quinazolin-4-yl-aminobenzenesulfonamide as potential antitumor agents.

Wed, 06 Jan 2016 00:00:00 +0100

Authors: Alafeefy AM, Ahmad R, Abdulla M, Eldehna WM, Al-Tamimi AS, Abdel-Aziz HA, Al-Obaid O, Carta F, Al-Kahtani AA, Supuran CT Abstract Carbonic anhydrases (CA I, II, IX and XII) are known to be highly expressed in various human malignancies. CA IX is overexpressed in colorectal cancer specifically in hereditary nonpolyposis colorectal cancer. Inhibition of CA activity by small molecular CA inhibitor like sulphonamides, sulphonamide derivative (SU.D2) or HIF1a inhibitor Chetomin leads to inhibition of tumorigenesis. Eighteen new quinazolin-4-sulfonamide derivatives were prepared and characterized by means of IR, NMR and mass spectra. Certain selected derivatives were tested for their ability to inhibit four isoforms of the metalloemzyme CA, namely, CA I, CA II, CA IX and CA XII....



Chemoprevention of colorectal neoplasia

Mon, 21 Dec 2015 00:00:00 +0100

ConclusionsCurrently, there is not enough evidence to support the implementation of a chemopreventative agent for general use. However, there appears to be a role for aspirin in selected subgroups. (Source: ANZ Journal of Surgery)



Project for the National Program of Early Diagnosis of Endometrial Cancer Part II.

Tue, 15 Dec 2015 21:30:04 +0100

Discussion: Improving medical practice based on diagnostic algorithms and programs improves and increases the lifetime expectancy, due to the fact that endometrial cancer is early diagnosed and treated before it causes serious health problems or even death. Abbreviations: ASCCP = American Society for Colposcopy and Cervical Pathology, CT = Computerized Tomography, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, MSI = Microsatellites instability, MSI-H/ MSI-L = high (positive test)/ low (negative test) microsatellites instability, PCR = Polymerase chain reaction, MRI = Magnetic Resonance Imaging, SGO = Society of Gynecologic Oncologists, SHG = Sonohysterography, TVUS = Transvaginal ultrasound. PMID: 26664463 [PubMed - as supplied by publis...

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Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations.

Fri, 11 Dec 2015 00:00:00 +0100

Authors: Sijmons RH, Hofstra RM Abstract Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive Constitutional Mismatch Repair Deficiency syndrome. Both conditions are important to recognize clinically as their identification has direct consequences for clinical management and allows targeted preventive actions in mutation carriers. Lynch syndrome is one of the more common adult-onset hereditary tumor syndromes, with thousands of patients reported to date. Its tumor spectrum is well established and includes colorectal cancer, endometrial cancer...



Approaches to diagnose DNA mismatch repair gene defects in cancer.

Tue, 08 Dec 2015 00:00:00 +0100

Authors: Peña-Diaz J, Rasmussen LJ Abstract The DNA repair pathway mismatch repair (MMR) is responsible for the recognition and correction of DNA biosynthetic errors caused by inaccurate nucleotide incorporation during replication. Faulty MMR leads to failure to address the mispairs or insertion deletion loops (IDLs) left behind by the replicative polymerases and results in increased mutation load at the genome. The realization that defective MMR leads to a hypermutation phenotype and increased risk of tumorigenesis highlights the relevance of this pathway for human disease. The association of MMR defects with increased risk of cancer development was first observed in colorectal cancer patients that carried inactivating germline mutations in MMR genes and the disease was named as ...



Mouse models of DNA mismatch repair in cancer research.

Fri, 04 Dec 2015 00:00:00 +0100

Authors: Lee K, Tosti E, Edelmann W Abstract Germline mutations in DNA mismatch repair (MMR) genes are the cause of hereditary non-polyposis colorectal cancer/Lynch syndrome (HNPCC/LS) one of the most common cancer predisposition syndromes, and defects in MMR are also prevalent in sporadic colorectal cancers. In the past, the generation and analysis of mouse lines with knockout mutations in all of the known MMR genes has provided insight into how loss of individual MMR genes affects genome stability and contributes to cancer susceptibility. These studies also revealed essential functions for some of the MMR genes in B cell maturation and fertility. In this review, we will provide a brief overview of the cancer predisposition phenotypes of recently developed mouse models with target...



Project for the National Program of Early Diagnosis of Endometrial Cancer Part I.

Wed, 18 Nov 2015 20:14:32 +0100

DISCUSSION: Improving medical practice based on diagnostic algorithms addresses the four risk groups, by improving information system reporting and record keeping. Improving addressability cases by increasing the health education of the population will increase the rate of diagnosis of endometrial cancer in the early stages of the disease. ABBREVIATIONS: ACOG = American Society of Obstetricians and Gynecologists, ASCCP = American Society for Colposcopy and Cervical Pathology, PATT = Partial Activated Thromboplastin Time, BRCA = Breast Cancer Gene, CT = Computerized Tomography, IFGO = International Federation of Gynecology and Obstetrics, HLG = Hemoleucogram, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, BMI = Body Mass Index, INR = Inte...



Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients.

Wed, 18 Nov 2015 20:14:32 +0100

DISCUSSION: NDI score may have a role as a colorectal cancer-screening test in "medium risk" individuals. ABBREVIATIONS: DNA = deoxyribonucleic acid; CRC = colorectal cancer; EU = European Union; WHO = World Health Organization; FOBT = fecal occult blood test; CBMN = cytokinesis-blocked micronucleus assay; MN = micronuclei; NPB = nucleoplasmic bridges; NDI = Nuclear Division Index; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polypoid colorectal cancer; IBD = inflammatory bowel diseases; ROC = receiver operating characteristics; AUROC = area under the receiver operating characteristics curve. PMID: 26351547 [PubMed - in process] (Source: Journal of Medicine and Life)

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[Challenges for Urologists in the Care of Patients with Lynch Syndrome: Example of A Patient with Muir-Torre Syndrome, A Subtype of Lynch Syndrome].

Wed, 28 Oct 2015 00:00:00 +0100

We report on a patient with various types of LS-associated cancers and cancers without a known association with LS, who died from multifocal metastasis of urothelial cancer. This case report shows that close interdisciplinary cooperation is mandatory for the treatment of patients with complex diseases. PMID: 26509248 [PubMed - as supplied by publisher] (Source: Aktuelle Urologie)



Detection of DNA repair protein in colorectal cancer of patients up to 50 years old can increase the identification of Lynch syndrome?

Fri, 25 Sep 2015 00:00:00 +0100

Abstract The aim of this study was to compare the results of protein level of the DNA mismatch repair genes with the clinical diagnosis of Lynch syndrome according to the Amsterdam II criteria in patients 50 years and younger who underwent surgery for colorectal cancer. The subjects of analysis were 48 patients 50 years old and younger. Immunohistochemistry assays were performed to detect proteins from the DNA mismatch repair genes. Clinicopathological data and Amsterdam II criteria for the diagnosis of hereditary nonpolyposis colorectal cancer were obtained by analyzing medical records. Two (4 %) patients satisfied the Amsterdam II criteria for Lynch syndrome, and both presented levels of all of the studied mismatch repair proteins. A total of 13 (27 %) patients exhibited the...



Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.

Fri, 21 Aug 2015 00:00:00 +0100

Authors: Carethers JM, Stoffel EM Abstract Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somati...



Next-generation sequencing for genetic testing of familial colorectal cancer syndromes

Fri, 21 Aug 2015 00:00:00 +0100

Conclusions The multiplex NGS approach has the advantage of analyzing multiple genes in multiple samples simultaneously, requiring only a reduced number of Sanger sequences to resolve homopolymeric DNA regions not adequately assessed by NGS. The implementation of NGS approaches in routine diagnostics of familial CRC is cost-effective and significantly reduces diagnostic turnaround times. (Source: Hereditary Cancer in Clinical Practice)



Aspirin lowers risk of hereditary bowel cancer in obese people

Tue, 18 Aug 2015 13:00:00 +0100

ConclusionThis study followed up on a previous trial that found taking aspirin regularly reduced the risk of bowel cancer in people with the genetic condition Lynch syndrome (or HNPCC), which puts them at an increased risk of developing the disease. The study found being obese appears to further increase bowel cancer risk among people with this condition.It also found that BMI did not appear to have an effect on bowel cancer risk among those taking aspirin. While this might indicate that aspirin removes the effect of BMI, ideally a comparison of aspirin versus placebo in the different BMI groups is needed to further assess this. It is likely that the number of people in this trial who fell into the individual BMI categories was not large enough to show an effect.However, this trial may not...

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Diffuse large B-cell lymphoma with microsatellite instability developing in the setting of Muir-Torre variant hereditary non-polyposis colon cancer

Tue, 18 Aug 2015 00:00:00 +0100

We report a patient with a Muir–Torre variant HNPCC who subsequently developed DLBCL. An elderly patient with a history of Muir–Torre variant HNPCC presented with abdominal pain, worsening over the preceding 1–2 months, with associated weight loss of 5 kg. The past medical history included metachronous rectal, colonic adenocarcinomas, pancreatic and jejunal... (Source: Journal of Clinical Pathology)



Abstract 3902: MSS HNPCC frequently contain CNVs in chromatin regulators

Sun, 02 Aug 2015 00:00:00 +0100

CONCLUSIONS: Genetic aberrations in chromatin remodeling could contribute to the development of MSS HNPCCs.Note: This abstract was not presented at the meeting.Citation Format: WeiXiang Chen, Xia sheng, Jun Ding. MSS HNPCC frequently contain CNVs in chromatin regulators. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3902. doi:10.1158/1538-7445.AM2015-3902 (Source: Cancer Research)



Abstract 2745: Exome sequencing analysis of 41 patients with Familial Colorectal Cancer Type X (FCCTX)

Sun, 02 Aug 2015 00:00:00 +0100

Colorectal cancer (CRC) is the second most common cancer. About 10% of CRC are hereditary including familial adenomatous polyposis (FAP), hereditary non-polyposis colorectal cancer (HNPCC), and rare syndromes. While genetics of FAP and rare syndromes is well studied (APC, STK11, AXIN2), only ∼40-50% of HNPCC have identifiable DNA mismatch-repair gene defects. CRC cases fulfilling Amsterdam Criteria I for HNPCC with normal DNA mismatch repair and elevated risk of microsatellite-stable CRC are called Familial Colorectal Cancer Type X (FCCTX). Compared to HNPCC, FCCTX patients are older, with left-sided CRC, and frequent polyps. We hypothesize that FCCTX is a dominant Mendelian cancer syndrome with incomplete penetrance caused by rare, family-specific mutations in oncogenes and tumor suppre...



Abstract 3847: MSI status frequency, MSI-target genes mutation profile and ancestry proportions in Brazilian colorectal carcinoma patients

Sun, 02 Aug 2015 00:00:00 +0100

Conclusion: The MSI frequencies identified in Brazilian CRC patients are in agreement with the international literature. We identify altered MSI-target genes in MSI-H tumors samples with potential clinical impact. For while, the ancestry proportions not showed an important factor for MSI status in Brazilian CRC patients.Note: This abstract was not presented at the meeting.Citation Format: Gustavo N. Berardinelli, Cristovam Scapulatempo-Neto, Ronilson Duraes, Denise Peixoto-Guimaraes, Armando Melani, Rui Pereira, Rui Reis. MSI status frequency, MSI-target genes mutation profile and ancestry proportions in Brazilian colorectal carcinoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadel...



American Gastroenterological Association Institute Guideline on the Diagnosis and Management of Lynch Syndrome

Tue, 28 Jul 2015 00:00:00 +0100

This document presents the official recommendations of the American Gastroenterological Association (AGA) Institute on the diagnosis and management of Lynch syndrome. Lynch syndrome (previously referred to as hereditary nonpolyposis colorectal cancer syndrome) is the most common heritable colorectal cancer syndrome, accounting for 2% to 3% of colorectal cancers, and has an estimated prevalence in the general population of 1 in 440. Patients with Lynch syndrome have an estimated lifetime cumulative incidence of colorectal cancer up to 80% and endometrial cancer up to 60% and also have increased risks of other cancers, including stomach, small intestine, pancreas, biliary tract, ovary, urinary tract, and brain. (Source: Gastroenterology)

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Familial colorectal cancer risk may be lower than previously thought: A Danish cohort study

Mon, 27 Jul 2015 00:00:00 +0100

Conclusion Although the overall risk in FDRs of CRC patients in our study was comparable with the results of previous studies, the risk in families with multiple relatives with CRC or one CRC patient diagnosed young may be lower than reported previously. (Source: Cancer Epidemiology)



Papillary thyroid carcinoma (PTC) in Lynch syndrome: Report of two cases and discussion on Lynch syndrome behaviour and genetics

Mon, 27 Jul 2015 00:00:00 +0100

We present here two cases of papillary thyroid carcinoma (PTC) in patients affected by Lynch syndrome (LS). The first case is a 47-year-old woman with typical hereditary non-polyposis colorectal cancer (HNPCC) syndrome, reported with endometrial and ovarian carcinoma at age 43, and colon cancer at age 45. The patient underwent total thyroidectomy and central node dissection in 2007, at 47years old, with a histological diagnosis of PTC (T1aN1a). Molecular genetics showed a germ-line mutation of the MLH1 gene, 1858 G>T(E620X), with substitution of glycine with a stop codon at position 620. This mutation has pathogenetic significance and was considered responsible for the various tumours of the HNPCC spectrum. In particular, in the same kindred, spanning 5 generations, there were 5 mem...



Intraductal papillary mucinous neoplasm of the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer: A case report.

Tue, 07 Jul 2015 00:00:00 +0100

We report a case of intraductal papillary mucinous neoplasm (IPMN) originating from the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer (HNPCC). A 49-year-old woman had a past history of total colectomy and total hysterectomy with bilateral salpingo-oophorectomy due to colonic adenocarcinoma and endometrial adenocarcinoma 11 years ago. Her parents died from colonic adenocarcinoma and her sister died from colonic adenocarcinoma and endometrial adenocarcinoma. The clinician found an ileal mass with necrotic change and the mass increased in size from 1.7 cm to 2.2 cm during the past 2 years on computed tomography. It was surgically resected. Microscopically, the ileal mass showed heterotopic pancreas with IPMN high grade dysplasia. Immunohistochemical s...



Muir-Torre Syndrome and founder Mismatch Repair genes mutations: A long gone historical genetic challenge.

Wed, 01 Jul 2015 00:00:00 +0100

Authors: Ponti G, Manfredini M, Tomasi A, Pellacani G Abstract A "cancer predisposing syndrome" later labeled as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Lynch syndrome, was firstly described by Warthin, about one century ago. An increased predisposition to the development of multiple familial tumors is described as characteristic of this syndrome where visceral and cutaneous malignancies may appear at an early age namely endometrial, gastric, small bowel, ureteral and renal pelvis, ovarian, hepatobiliary tract, pancreatic, brain (Turcot Syndrome) and sebaceous glands (Muir-Torre Syndrome). The latter, a variant of Lynch Syndrome, is characterized by the presence of sebaceous skin adenomas, carcinomas and/or keratoachantomas associated to visceral malignancies. Both Ly...



Epidemioclinical Feature of Early-Onset Colorectal Cancer at-Risk for Lynch Syndrome in Central Iran.

Fri, 26 Jun 2015 23:46:07 +0100

CONCLUSIONS: Given the high prevalence of FCC (~1/4 of early-onset Iranian CRC patients), it is necessary to establish a comprehensive cancer genetic counseling and systematic screening program for early detection and to improve cancer prognosis among high risk families. PMID: 26107218 [PubMed - in process] (Source: Asian Pacific Journal of Cancer Prevention)

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Epigenetics could explain some Moroccan population colorectal cancers peculiarities: microsatellite instability pathway exploration

Wed, 24 Jun 2015 00:00:00 +0100

Conclusions: These results confirm the high occurrence of CRCs to young patients and the high frequency of rectal localizations in Moroccan population. They mostly show an absence of BRAF mutation, supposing a rarity of MLH1 promoter hypermethylation pathway, which may even partially explain the CRC peculiarities in our context.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5868184711716884 (Source: Diagnostic Pathology)



Family with MSH2 mutation presenting with keratoacanthoma and precancerous skin lesions

Tue, 16 Jun 2015 00:00:00 +0100

We report a family with an MSH2 mutation c.1126_1127delTT (p.Leu376Thrfs*12). A 46‐year‐old male proband developed KA with sebaceous differentiation, colon cancer and gastric cancer, and fulfilled the diagnostic criteria for MTS. His 80‐year‐old mother, diagnosed with HNPCC, presented with multiple gastrointestinal tract cancers, Bowen's disease and actinic keratosis. Immunostaining revealed attenuated MSH2 protein expression in KA, as well as in Bowen's disease and actinic keratosis lesions. These findings suggest that MMR gene abnormality is also critical in the development of benign or malignant cutaneous tumors such as actinic keratosis and Bowen's disease in MTS/HNPCC patients. (Source: The Journal of Dermatology)



Advances in the study of Lynch syndrome in China.

Sun, 14 Jun 2015 00:00:00 +0100

Authors: Lu JY, Sheng JQ Abstract Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers due to inherited mutations in mismatch repair (MMR) genes. During the last decades, there have been great advances in research on Chinese Lynch syndrome. This review mainly focuses on the genetic basis, clinicopathologic features, diagnosis, intervention, chemoprevention, and surveillance of Lynch syndrome in China. In addition to frequently altered MMR genes, such as MLH1, MSH2, MSH6, and MLH3, other MMR-associated genes, such as those encoding human exonuclease 1, transforming growth factor β receptor 2, and alanine aminopeptidase, metastasis-associated protein 2, adenom...



Risk Factors Associated with Colorectal Cancer in a Subset of Patients with Mutations in MLH1 and MSH2 in Taiwan Fulfilling the Amsterdam II Criteria for Lynch Syndrome

Mon, 08 Jun 2015 00:00:00 +0100

Conclusion The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers. (Source: PLoS One)



Germline Mutations in Cause Hereditary Colorectal Cancer by Impairing DNA Repair

Thu, 04 Jun 2015 00:00:00 +0100

Identification of genes associated with hereditary cancers facilitates management of patients with family histories of cancer. We performed exome sequencing of DNA from 3 individuals from a family with colorectal cancer who met the Amsterdam criteria for risk of hereditary nonpolyposis colorectal cancer. These individuals had mismatch repair-proficient tumors and each carried nonsense variant in the FANCD2/FANCI-associated nuclease 1 gene (FAN1), which encodes a nuclease involved in DNA inter-strand cross-link repair. (Source: Gastroenterology)

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[In Process Citation].

Mon, 01 Jun 2015 00:00:00 +0100

Authors: Herr G, Szenes M, Hohl G, Vinkler ME, Tüske G, Horváth J, Nagy G, Tihanyi M, Széll M, Nagy N, Gasztonyi B Abstract Muir-Torre syndrome is a rare genodermatosis with autosomal dominant inheritance. The syndrome is considered to be a subtype of the hereditary nonpolyposis colorectal cancer (or Lynch-syndrome). In two-third of the cases, it develops as the consequence of germline mutations in mismatch-repair genes - most commonly MutS Homolog-2 and MutL Homolog-1. Its diagnosis can be established if at least one sebaceous tumor (sebaceoma, sebaceous adenoma, epithelioma, carcinoma or basal-cell carcinoma with sebaceous differentiation) and/or keratoacanthoma and at least one internal neoplasm are present. Here the authors present the history of a 52-year-old man with multi...



Survival in familial colorectal cancer: a Danish cohort study

Mon, 11 May 2015 23:23:25 +0100

Abstract The monogenic Lynch syndrome (LS) is associated with better survival in colorectal cancer (CRC) patients. Whether family history of CRC affects CRC prognosis in general remains unclear. We evaluated overall mortality in a Danish cohort of CRC patients comparing patients with a family history (FHpos) to those without (FHneg) with focus on patients from non-syndromic families, thus FHpos patients were further divided into a non-syndromic group (FHNS) and a HNPCC/LS group (FHHNPCC). We included CRC patients diagnosed 1995–1998. First degree relatives were identified using Danish population registries and family history was obtained by linkage to Danish medical registries. 1- and 5-year mortality were evaluated using the Kaplan–Meier method and Cox regression, with adjust...



Segmental vs extended colectomy in the management of hereditary nonpolyposis colorectal cancer: a systematic review and meta‐analysis

Tue, 21 Apr 2015 00:00:00 +0100

ConclusionThe optimal surgical approach in the management of HNPCC remains unclear. More adenomas and cancers occur after SC than after TC but there certainly is no evidence to suggest that more radical surgery leads to improved survival. (Source: Colorectal Disease)



HNPCC-Associated Pheochromocytoma: Expanding the Tumor Spectrum

Fri, 17 Apr 2015 09:15:04 +0100

No abstract available (Source: Pancreas)



Novel quality indicators for metastatic colorectal cancer management identify significant variations in these measures across treatment centers in Australia.

Tue, 14 Apr 2015 00:00:00 +0100

CONCLUSIONS: We have defined a novel set of mCRC QCIs and have demonstrated wide variation in the quality of care of mCRC across multiple Australian sites. With further validation to confirm a direct correlation between QCI and patient outcomes, these QCIs could be applied to improve the quality of care received by all mCRC patients. PMID: 25871458 [PubMed - as supplied by publisher] (Source: Clinical Colorectal Cancer)

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Novel quality indicators for metastatic colorectal cancer management identify significant variations in these measures across treatment centers in Australia

Tue, 14 Apr 2015 00:00:00 +0100

ConclusionsWe have defined a novel set of mCRC QCIs and have demonstrated wide variation in the quality of care of mCRC across multiple Australian sites. With further validation to confirm a direct correlation between QCI and patient outcomes, these QCIs could be applied to improve the quality of care received by all mCRC patients. (Source: Asia-Pacific Journal of Clinical Oncology)



Hereditary Non-polyposis Colorectal Cancer: Prevention and Therapeutic Options

Thu, 19 Mar 2015 00:00:00 +0100

Abstract Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common hereditary colorectal cancer (CRC) syndrome. The first and foremost preventive measure is to identify patients with LS among CRC patients. This requires the screening of colorectal cancer through polymerase chain reaction-based microsatellite instability (MSI) testing or immunohistochemistry to look for a loss of expression of one of the mismatch repair (MMR) proteins and the referral of selected patients to genetic counseling. In LS patients, annual or biannual complete colonoscopy with chromoendoscopy is the only validated way to significantly reduce mortality related to CRC with the greatest quality-adjusted life expectancy benefit compared with prophylactic surger...



Defining the Adenoma Burden in Lynch Syndrome

Tue, 10 Mar 2015 02:58:27 +0100

CONCLUSIONS: Although 10 or more adenomas prompt testing for polyposis syndromes, Lynch syndrome should also be considered in the differential diagnosis. (Source: Diseases of the Colon and Rectum)



Resources to increase genetics and genomics capacity of oncology nurses.

Sun, 01 Mar 2015 00:00:00 +0100

Authors: Aiello LB Abstract Since the completion of the Human Genome Project (HGP) in 2003, the understanding of genetics and its influence on disease, particularly cancer, has increased dramatically. The initial focus after the completion of HGP was on identifying single-gene disorders, such as many hereditary cancer syndromes (e.g., BRCA1, BRCA2, HNPCC). As research continues, the major impact that genetics and genomics have across the healthcare continuum is only beginning to become clear (Pestka, Burbank, & Junglen, 2010; Thompson & Brooks, 2011). More specifically, genetics and genomics play a role in disease risk and prevention, carcinogenesis, diagnosis, prognosis, treatment selection, use of targeted agents, pain management, and end-of-life care. The implications of...



Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer

Thu, 26 Feb 2015 10:17:07 +0100

CONCLUSIONSThe results of the current study confirmed cases of LS in approximately 1.0% of CRC samples and reflects the efficacy of screening among MSI‐H cases that lack BRAF mutations. This comprehensive study from Saudi Arabia will help in implementing a universal screening/reflex testing strategy in a clinical setting in Saudi Arabia and in conducting a national screening program that benefits both patients and their relatives. Cancer 2015. © 2015 American Cancer Society. (Source: Cancer)

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Relationship between smoking and multiple colorectal cancers in patients with Japanese Lynch syndrome: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum

Wed, 25 Feb 2015 00:00:00 +0100

The positive correlation between smoking and cancer risk is well estimated in sporadic colorectal cancer, whereas little is known with regard to Lynch syndrome-associated colorectal cancer. A total of 118 familial colorectal cancer patients from the Hereditary Nonpolyposis Colorectal Cancer Registry and Genetic Testing Project of the Japanese Society for Cancer of the Colon and Rectum, were assessed to determine whether smoking alters the incidence of multiple colorectal cancers. In male patients with Lynch syndrome (n = 29), the incidence of multiple colorectal cancers in patients who had ever smoked (smoking duration: median of 19 years) was higher than that in those who never smoked (58.8% vs. 10.0%, P = 0.02). The cumulative risk for metachronous colorectal cancer was significantly hig...



Lynch Syndrome: A Primer for Urologists and Panel Recommendations

Sat, 21 Feb 2015 00:00:00 +0100

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer, is a common genetic disease. The predisposition of LS to urologic cancers, particularly upper tract urothelial carcinoma (UTUC), is underappreciated. Urologists may be involved in several aspects of care involving LS including identification of undiagnosed cases, surveillance of established LS patients or screening family members, and treating LS patients who develop UTUC. In this review, we seek to increase awareness in the urologic community about LS and provide some guidance where little currently exists. (Source: The Journal of Urology)



Mismatch Repair mRNA and Protein Expression in Intestinal Adenocarcinoma in Sika Deer (Cervus nippon) Resembling Heritable Non-polyposis Colorectal Cancer in Man

Fri, 13 Feb 2015 00:00:00 +0100

Publication date: Available online 9 February 2015 Source:Journal of Comparative Pathology Author(s): H. Jahns , J.A. Browne Intestinal adenocarcinomas seen in an inbred herd of farmed sika deer (Cervus nippon) morphologically resembled human hereditary non-polyposis colorectal cancer (HNPCC). Features common to both included multiple de novo sites of tumourigenesis in the proximal colon, sessile and non-polyposis mucosal changes, the frequent finding of mucinous type adenocarcinoma, lymphocyte infiltration into the neoplastic tubules and Crohn's-like lymphoid follicles at the deep margin of the tumour. HNPCC is defined by a germline mutation of mismatch repair (MMR) genes resulting in their inactivation and loss of expression. To test the hypothesis that similar MMR gene inactivation oc...



Genetic Diagnosis of High-Penetrance Susceptibility for Colorectal Cancer (CRC) Is Achievable for a High Proportion of Familial CRC by Exome Sequencing [Genetic Testing for Cancer]

Fri, 06 Feb 2015 00:00:00 +0100

Conclusion A genetic diagnosis is feasible in a high proportion of familial CRC. Mainstreaming such analysis in clinical practice should enable the medical management of patients and their families to be optimized. Findings suggest CRC screening of POLE and POLD1 mutation carriers should be comparable to that afforded to those at risk of HNPCC. Although the risk of CRC associated with unexplained familial CRC is in general moderate, in some families the risk is substantive and likely to be the consequence of unidentified genes, as exemplified by POLE and POLD1. Our findings have utility in the design of genetic analyses to identify such novel CRC risk genes. (Source: Journal of Clinical Oncology)



Comparison of clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients with colorectal cancer: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum

Sat, 31 Jan 2015 00:00:00 +0100

Conclusion A significant difference in extracolonic Lynch syndrome-associated cancer was evident between suspected familial colorectal cancer type X and Lynch syndrome. (Source: Japanese Journal of Clinical Oncology)

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Ideal colonoscopic surveillance intervals to reduce incidence of advanced adenoma and colorectal cancer

Thu, 22 Jan 2015 00:00:00 +0100

ConclusionsMost family history categories did not confer excess risk above personal history of advanced neoplasia. A prior cancer poses less of a risk than a prior advanced adenoma. Based on our models, a person with an advanced adenoma should be scheduled for colonoscopy at 3 years, corresponding to a 15% risk of advanced neoplasia for a male <56. Guidelines should be updated that uses a 15% risk as a benchmark for calculating surveillance intervals. (Source: Journal of Gastroenterology and Hepatology)



Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome

Mon, 19 Jan 2015 15:57:50 +0100

ConclusionIn Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects. (Source: European Journal of Neurology)



Management of ovarian and endometrial cancers in women belonging to HNPCC carrier families: review of the literature and results of cancer risk assessment in Polish HNPCC families

Fri, 16 Jan 2015 00:00:00 +0100

Conclusions Due to the increased risk of OC and absence of any benefit from gynecological screening reported in the literature it is recommended that prophylactic oophorectomy for female carriers of MMR mutations after 35 year of age should be considered as a risk reducing option. Annual transvaginal ultrasound supported by CA125 or HE4 marker testing should be performed after prophylactic surgery in these women. Due to the high risk of EC it is reasonable to offer, after the age of 35 years, annual clinical gynecologic examinations with transvaginal ultrasound supported by routine aspiration sampling of the endometrium for women from either LS or HNPCC families. An alternative option, which could be taken into consideration for women preferring surgical prevention,...



Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas

Sat, 20 Dec 2014 00:00:00 +0100

In conclusion, a PPAP was identified in a substantial number of polyposis and familial colorectal cancer patients. Screening for polymerase proofreading mutations should therefore be considered, particularly in unexplained familial cases. The present study broadens the phenotypic spectrum of PPAP to duodenal adenomas and carcinomas, and identified novel, potentially pathogenic variants in four polymerase genes. This article is protected by copyright. All rights reserved. (Source: International Journal of Cancer)



Tumoral expression of nuclear cofactor FHL2 is associated with lymphatic metastasis in sporadic but not in HNPCC-associated colorectal cancer

Thu, 18 Dec 2014 00:00:00 +0100

Conclusions We recently demonstrated that enhanced nuclear FHL2 expression in tumor stroma of sporadic colon cancer is associated with lymphatic metastasis. The results of the present study indicate a synergistic effect of nuclear cofactor FHL2 in tumor cells as well as in peritumoral stroma cells promoting lymphatic metastasis in sporadic CRC. As HNPCC-associated tumors did not show a significant association between tumoral nuclear FHL2 expression and lymphatic metastasis we speculate, that the intensive lymphocytic immune response in HNPCC precludes a direct contact of tumor cells and stromal cells resulting in reduced lymphatic spread. (Source: Pathology Research and Practice)

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Segmental versus extended colectomy in the management of HNPCC; a systematic review and meta‐analysis

Tue, 16 Dec 2014 08:11:44 +0100

ConclusionsThe optimal surgical approach in the management of HNPCC remains unclear. More adenomas and cancers occur after segmental colectomy than after total colectomy but there certainly isn't evidence to suggest that more radical surgery leads to improved survival.This article is protected by copyright. All rights reserved. (Source: Colorectal Disease)



Abstract 18: Molecular characterization of Brazilian patients suspected for Lynch syndrome

Fri, 12 Dec 2014 00:00:00 +0100

Lynch syndrome (LS), former known as Hereditary Non Polyposis Colorectal cancer (HNPCC), accounts for 3-5% of all colorectal cancers (CRC) and is inherited in an autossomal dominant fashion. This syndrome is characterized by early CRC onset, high incidence of tumors in the ascending colon, excess of synchronous and metachronous tumors, and accelerated transition adenoma-carcinoma (2-3 years). Nowadays, LS is regarded of patients who carry deleterious germline mutations in one of the five Mismatch repair genes, such as MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), post-meiotic segregation increased 1 (PMS1) or post-meiotic segregation increased 2 (PMS2). In order to characterize Brazilian patients suspect for LS, we assessed the frequency of germline point mutations i...



Tumoural expression of nuclear cofactor FHL2 is associated with lymphatic metastasis in sporadic but not in HNPCC-associated colorectal cancer

Fri, 12 Dec 2014 00:00:00 +0100

Conclusions We recently demonstrated that enhanced nuclear FHL2 expression in tumour stroma of sporadic colon cancer is associated with lymphatic metastasis. The results of the present study indicate a synergistic effect of nuclear cofactor FHL2 in tumour cells as well as in peritumoural stroma cells promoting lymphatic metastasis in sporadic CRC. As HNPCC-associated tumours did not show a significant association between tumoural nuclear FHL2 expression and lymphatic metastasis we speculate, that the intensive lymphocytic immune response in HNPCC precludes a direct contact of tumour cells and stromal cells resulting in reduced lymphatic spread. (Source: Pathology Research and Practice)



Tumoral expression of nuclear cofactor FHL2 is associated with lymphatic metastasis in sporadic but not in HNPCC-associated colorectal cancer.

Thu, 11 Dec 2014 00:00:00 +0100

CONCLUSIONS: We recently demonstrated that enhanced nuclear FHL2 expression in tumor stroma of sporadic colon cancer is associated with lymphatic metastasis. The results of the present study indicate a synergistic effect of nuclear cofactor FHL2 in tumor cells as well as in peritumoral stroma cells promoting lymphatic metastasis in sporadic CRC. As HNPCC-associated tumors did not show a significant association between tumoral nuclear FHL2 expression and lymphatic metastasis we speculate, that the intensive lymphocytic immune response in HNPCC precludes a direct contact of tumor cells and stromal cells resulting in reduced lymphatic spread. PMID: 25554651 [PubMed - as supplied by publisher] (Source: Pathology, Research and Practice)



Erratum to: Clinicopathological and genetic features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC)

Thu, 04 Dec 2014 00:00:00 +0100

(Source: Medical Oncology)

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Muir-torre syndrome.

Sun, 30 Nov 2014 11:15:03 +0100

Authors: Bhaijee F, Brown AS Abstract Muir-Torre syndrome (MTS) is a rare autosomal-dominant genodermatosis characterized by sebaceous neoplasms and one or more visceral malignancies. Sebaceous tumors include sebaceous adenoma and carcinoma, which may be solitary or multiple. Visceral malignancies most often arise in the colorectum and endometrium. Because a subset of patients with phenotypic MTS will have germline mutations in the DNA mismatch repair genes hMSH2 and hMLH1, MTS is considered a phenotypic subtype of Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome), in which inherited defects in DNA mismatch repair genes result in microsatellite instability. Pathologists have an important role in the early detection and initial diagnosis of MTS: ident...



Tumour MLH1 promoter region methylation testing is an effective prescreen for Lynch Syndrome (HNPCC)

Mon, 17 Nov 2014 00:00:00 +0100

Conclusions Quantitative MLH1 promoter region methylation using pyrosequencing is superior to BRAF codon 600 mutation status in identifying constitutional mutations in mismatch repair deficient tumours. (Source: Journal of Medical Genetics)



MutS Homologues hMSH4 and hMSH5: Genetic Variations, Functions, and Implications in Human Diseases.

Sat, 15 Nov 2014 00:15:43 +0100

Authors: Clark N, Wu X, Her C Abstract The prominence of the human mismatch repair (MMR) pathway is clearly reflected by the causal link between MMR gene mutations and the occurrence of Lynch syndrome (or HNPCC). The MMR family of proteins also carries out a plethora of diverse cellular functions beyond its primary role in MMR and homologous recombination. In fact, members of the MMR family of proteins are being increasingly recognized as critical mediators between DNA damage repair and cell survival. Thus, a better functional understanding of MMR proteins will undoubtedly aid the development of strategies to effectively enhance apoptotic signaling in response to DNA damage induced by anti-cancer therapeutics. Among the five known human MutS homologs, hMSH4 and hMSH5 form a unique ...



Abstract A27: BLM overexpression promotes tumorigenicity in an azoxymethane/dextran sulfate (AOM/DSS) murine model of intestinal cancer

Thu, 13 Nov 2014 00:00:00 +0100

The role of genomic instability in colorectal cancer susceptibility is well established by studies of hereditary non-polyposis colon cancer (HNPCC), its associated disruption of DNA mismatch repair, and other DNA repair deficiencies that predispose to colon cancer. DNA repair deficiency that results in loss of capacity to maintain the genome leads to increased mutation or chromosome instability that in turn increases tumor formation. In some recent experiments using mouse models of cancer, deletion of genomic housekeeping genes promoted tumorigenesis. The Blm gene encodes a RecQ helicase that represses aberrant homologous recombination. Previous experiments using ApcMin/+ mice showed that a heterozygous Blm mutation increased intestinal tumor formation and tumor dysplasia. Conversely, mice...



DNA repair genes and prognosis in sporadic forms of urothelial carcinoma of the upper urinary tract

Wed, 22 Oct 2014 00:00:00 +0100

Conclusion In our experience, the inactivation of hPMS2 or hMLH1 is an independent marker of good prognosis and occurs in a quarter of sporadic UTUC cases. The immunohistochemical study of these patients can be used to assess the screening of hidden forms of Lynch syndrome. (Source: Actas Urologicas Espanolas)

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Low Frequency of HNPCC-Associated Microsatellite Instability and Aberrant MMR Protein Expression in Early-Onset Bladder Cancer.

Tue, 21 Oct 2014 14:45:14 +0100

CONCLUSIONS: In young patients with bladder tumors, MSI and defects in MMR protein expression were not more frequent than in a series of consecutive bladder tumors. Most bladder tumors in young patients are not to be attributed to Lynch syndrome. PMID: 25319978 [PubMed - in process] (Source: American Journal of Clinical Pathology)



P1-11-1 * IMPORTANCE TO CLARIFY GERMLINE hMLH1 K618A MISSENSE MUTATION FOR CLINICAL SURVEILLANCE AND GENETIC COUNSELING

Sun, 19 Oct 2014 00:00:00 +0100

Colorectal cancer (CRC) is the third common cancer and the fourth leading cause of cancer death worldwide. Subproportion CRC with defect function in one of the mismatch repair gene (MMR) are classed as inherited non-polyposis colorectal cancer (HNPCC) later called Lynch syndrome (LS). Disease causing germline mutations have so far been identified in five MMR genes. Among other MMR genes, germline mutations in hMLH1 account up to 50% LS patients and lead to increased risk of cancer development. hMLH1 K618A variant was first identified in our lab and was considered as a disease causing pathogenic alteration, our further investigation also support our previous findings. Although this variant has been investigated intensively during past decade, however the pathogenicity still remain unclear d...



Abstract 1910: Evolution of preleukemia stem cells to lymphoma initiating cells requires thymus in msh2-/- mice

Tue, 30 Sep 2014 00:00:00 +0100

In this study, we use MSH2-/- mice as a model to investigate the existence of PLSC and the evolution of PLSC to LIC. Using bone marrow transplantation, we found that limiting dilutions of MSH2-/- HSCs from young mice are able to reconstitute lethally irradiated wild-type recipients, and contribute to development of multiple hematopoietic lineages. However, all the recipients develop thymic lymphomas after a latency of 3-4 months post transplantation. Transplantation of different fractions of bone marrow cells or thymocytes from young MSH2-/- mice showed that only the HSC enriched fraction leads to lymphoma development. The lymphomas are transplantable, limiting dilution experiments showed that even 40 lymphoma cells could initiate T cell leukemia in sublethally irradiated secondary recipie...



Statement on risk assessment for inherited gynecologic cancer predispositions.

Wed, 17 Sep 2014 00:00:00 +0100

Authors: Lancaster JM, Powell CB, Chen LM, Richardson DL, SGO Clinical Practice Committee Abstract Women with germline mutations in the cancer susceptibility genes, BRCA1 or BRCA2, associated with Hereditary Breast & Ovarian Cancer syndrome, have up to an 85% lifetime risk of breast cancer and up to a 46% lifetime risk of ovarian, tubal, and peritoneal cancers. Similarly, women with mutations in the DNA mismatch repair genes, MLH1, MSH2, MSH6, or PMS2, associated with the Lynch/Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, have up to a 40-60% lifetime risk of both endometrial and colorectal cancers as well as a 9-12% lifetime risk of ovarian cancer. Mutations in other genes including TP53, PTEN, and STK11 are responsible for hereditary syndromes associated with g...

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Clinicopathological and genetic features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC)

Sat, 13 Sep 2014 00:00:00 +0100

Abstract The aim of this study was to investigate the clinical value of different criteria and to understand the relationship between genotype and phenotype in Chinese hereditary nonpolyposis colorectal cancer (HNPCC). A total of 116 unrelated probands of suspected HNPCC families from the Fudan Colorectal Registry were studied. A total of 32, 28, and 56 families fulfilled the Amsterdam criteria, the Fudan criteria and the revised Bethesda guideline, respectively. Direct DNA sequencing of all exons of hMSH2 and hMLH1 genes were performed on all 116 samples. Mutations and clinicopathological features were compared between the groups. Thirty-two pathological germline mutations were identified. Out of 32 mutations, 16 were located at hMLH1 and 16 at hMSH2. The sensitivity of Amsterda...



Familial Pancreatic Cancer: Challenging Diagnostic Approach and Therapeutic Management

Mon, 01 Sep 2014 00:00:00 +0100

Conclusions However, the optimal age of initial screening remains undefined. Furthermore, a multidisciplinary assessment is required to determine whether surgical interventions should be performed at high-volume specialty centers. The aim of this study is to collect all the recent information considering the genetic basis, screening protocols, and treatment of FPC in order to provide an update on the current contemporary concepts of therapeutic management of the disease. (Source: International Journal of Gastrointestinal Cancer)



Colonoscopy screening compliance and outcomes in patients with Lynch Syndrome

Mon, 01 Sep 2014 00:00:00 +0100

ConclusionOverall 68% of colonoscopies were on time. The incidence of colorectal cancer was greatly reduced by screening but remained significant. Lynch syndrome patients need pro‐active surveillance management.This article is protected by copyright. All rights reserved. (Source: Colorectal Disease)



Covering the Cover

Thu, 21 Aug 2014 18:34:19 +0100

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is the most common form of inherited colon cancer susceptibility. In most cases, it is characterized by mutations in the DNA mismatched repair genes, MSH2, MLH1, PMS1, MSH6, or MLH3. The Amsterdam criteria is a clinical guideline used to identify HNPCC in kindreds, and includes ≥3 relatives (one of whom is a first-degree relative and for whom familial adenomatous polyposis has been ruled out), HNPCC involving ≥2 generations, and ≥1 cancer that was diagnosed before the age of 50. (Source: Gastroenterology)



Defining HNPCC and Lynch syndrome: what's in a name?

Sun, 03 Aug 2014 00:00:00 +0100

Dear Sir, In June 2013, the Mallorca Group published revised guidelines for the clinical management of Lynch syndrome.1 In the title, HNPCC (Hereditary NonPolyposis Colorectal Cancer) is equated with Lynch syndrome, continuing a misuse of terms that has fuelled confusion for many years. The two terms describe different, although overlapping, diseases: the distinction is critical to an accurate understanding of hereditary colorectal cancer. HNPCC is defined clinically, usually as families satisfying Amsterdam I or II criteria.2 Lynch syndrome is defined genetically, by the presence of a germline mutation in DNA mismatch repair (MMR) or EPCAM genes.3 Not all HNPCC families have Lynch syndrome and not all Lynch syndrome families have HNPCC. To determine the extent of the misuse of terms, we s...

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A very low incidence of BRAF mutations in Middle Eastern colorectal carcinoma

Tue, 08 Jul 2014 00:00:00 +0100

Conclusion: Our results highlight the low incidence of BRAF mutations and CIMP in CRC from Saudi Arabia. This could be attributed to ethnic differences and warrant further investigation to elucidate the effect of other environmental and genetic factors. These findings indirectly suggest the possibility of a higher incidence of familial hereditary colorectal cancers especially Hereditary non polyposis colorectal cancer (HNPCC) syndrome /Lynch Syndrome (LS) in Saudi Arabia. (Source: Molecular Cancer)



DNA repair genes and prognosis in sporadic forms of urothelial carcinoma of the upper urinary tract.

Fri, 20 Jun 2014 00:00:00 +0100

CONCLUSION: In our experience, the inactivation of hPMS2 or hMLH1 is an independent marker of good prognosis and occurs in a quarter of sporadic UTUC cases. The immunohistochemical study of these patients can be used to assess the screening of hidden forms of Lynch syndrome. PMID: 24958312 [PubMed - as supplied by publisher] (Source: Actas Urologicas Espanolas)



Microsatellite testing in colon cancer.

Thu, 01 May 2014 00:00:00 +0100

Authors: Mahon SM Abstract Significant progress has been made in understanding the molecular genetic basis of colorectal cancer (CRC). That information is paving the way to understanding the genetic basis of other tumors, as well. Oncology nurses should anticipate the routine integration of this information and testing of CRC tumors to understand the molecular basis of the disease in clinical practice. Molecular testing can lead to the identification of families at risk for hereditary cancer syndromes, particularly Lynch syndrome, which sometimes is referred to as hereditary nonpolyposis colorectal cancer. Knowledge of the genetic basis of CRC also contributes valuable information aimed at selecting appropriate and effective targeted therapy. PMID: 24769599 [PubMed - in proces...



A de novo germline mutation of APC for inheritable colon cancer in a Chinese family using multigene next generation sequencing.

Sat, 12 Apr 2014 00:00:00 +0100

Authors: Zhang Y, Lu G, Hu Q, Wang X, Li C, Mao Y, Cui M Abstract Inheritable Colorectal cancers (CRC) accounted for about 20% of the CRC cases, such as hereditary nonpolyposis colorectal cancer (HNPCC), Gardner syndrome and familial adenomatous polyposis (FAP). A four-generation Han Chinese family was found affected with polyposis in colons. Inferred form the pedigree structure, the disease in this family showed an autosomal dominant inheritance model. To locate the causal mutations in this family, genomic DNAs were extracted and the next generation sequencing for 5 genes relating to colon cancer performed by Ion Torrent Personal Genome Machine with a 314 chip. The reads were aligned with human reference genome hg19 to call variants in the 5 genes. After analysis, 14 variants were...



Determining eligibility for and preparation to kidney transplantation of a patient with Lynch syndrome - a case report and literature review.

Sun, 16 Mar 2014 16:15:36 +0100

Conclusions: The risk of recurrence or new development of cancer related to immunosuppressive treatment should be considered on a case-by-case basis. In patients with a history or high risk of cancer, immunosuppression protocols based on the m-TOR pathway inhibitors should be used, if possible. Oncological surveillance and early detection of new cancer lesions are also important. PMID: 24614524 [PubMed - in process] (Source: Annals of Transplantation)

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The results of gynecologic surveillance in families with hereditary nonpolyposis colorectal cancer.

Thu, 13 Mar 2014 00:00:00 +0100

CONCLUSION: Based on 19,334 women years of EC-surveillance, our analysis provides a thorough estimation of the EC risk in women with an MMR mutation, or suspected of having Lynch syndrome. We conclude that EC surveillance should only be targeted to MMR-mutation carriers. PMID: 24631699 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)



Quest Diagnostics Expands Hereditary Cancer Screening Offering with Lynch Syndrome Blood and Biopsy Testing for Colorectal Cancer

Wed, 26 Feb 2014 15:47:08 +0100

Company Supports March's Colorectal Cancer Awareness Month by Participating in the One Million Strong Screening Event in New York City on March 3 MADISON, N.J., Feb. 26, 2014 -- (Healthcare Sales & Marketing Network) -- Quest Diagnostics (DGX), the wor... Diagnostics, Oncology, Product LaunchQuest Diagnostics, Lynch syndrome, hereditary nonpolyposis colorectal cancer (Source: HSMN NewsFeed)



Should we systematically Screen for Lynch syndrome in Patients with upper urinary tract carcinoma?

Fri, 21 Feb 2014 00:00:00 +0100

Authors: Olagui GS, Pignot G, Rouquette A, Vieillefond A, Amsellem-Ouazana D, Longchamps NB, Radenen B, Zerbib M, Terris B Abstract The data describing the urologic extracolonic cancers associated with Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) are variable. The aim of our study was to establish the frequency of mutations in mismatch repair (MMR) genes in patients with upper urinary tract transitional cell carcinoma (UUT-TCC) and to evaluate the clinical benefits of a systematic screening. Specimen blocks were obtained from 146 patients treated for UUT-TCC in our center. Clinicopathological characteristics and survival data of patients were collected (median follow-up = 42.5 months). Immunohistochemistry was performed by tissue microarray (TMA), in orde...



Lynch Syndrome from a surgeon perspective: retrospective study of clinical impact of mismatch repair protein expression analysis in colorectal cancer patients less than 50 years old

Mon, 17 Feb 2014 00:00:00 +0100

Conclusions: The present study confirms that preoperative knowledge of MMR proteins expression in colorectal cancer patients would allow correct staging, more extended colonic resection, specific follow-up and familial screening. (Source: BMC Surgery)



Evaluating the performance of clinical criteria for predicting mismatch repair gene mutations in Lynch syndrome: A comprehensive analysis of 3671 families

Tue, 03 Dec 2013 05:00:00 +0100

Abstract Carriers of mismatch repair (MMR) gene mutations have a high lifetime risk for colorectal and endometrial cancers, as well as other malignancies. As mutation analysis to detect these patients is expensive and time‐consuming, clinical criteria and tumour‐tissue analysis are widely used as pre‐screening methods. The aim of our study was to evaluate the performance of commonly applied clinical criteria (the Amsterdam I and II Criteria, and the original and revised Bethesda Guidelines) and the results of tumour‐tissue analysis in predicting MMR gene mutations. We analyzed 3671 families from the German HNPCC Registry and divided them into nine mutually exclusive groups with different clinical criteria. A total of 680 families (18.5%) were found to have a pathogenic MMR gene mut...

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Molecular Diagnostics in Colorectal Carcinoma

Tue, 26 Nov 2013 11:15:06 +0100

Molecular pathogenesis and classification of colorectal carcinoma are based on the adenoma-carcinoma sequence in the Vogelstein model, serrated polyp pathway, and microsatellite instability. The genetic basis for hereditary nonpolyposis colorectal cancer is based on detection of genetic mutations. Genetic testing for Lynch syndrome includes microsatellite instability, methylator phenotyping, BRAF mutation, and molecular testing. Molecular makers include quantitative multigene reverse transcriptase–polymerase chain reaction assay and KRAS and BRAF mutation analysis. Potential biomarkers include one-step nucleic acid amplification and epigenetic inactivation of endothelin 2 and endothelin 3 in colon cancer. Molecular screening approaches in colorectal cancer using stool DNA are under inves...



Prevalence of occult gynecologic malignancy at the time of risk reducing and nonprophylactic surgery in patients with Lynch syndrome.

Tue, 05 Nov 2013 05:00:00 +0100

CONCLUSIONS: Patients should be counseled about the risks of finding gynecologic cancer at the time of prophylactic or non-prophylactic surgery for Lynch syndrome and HNPCC, and the potential need for additional surgery. PMID: 24211399 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)



Dominant Mutations in S. cerevisiae PMS1 Identify the Mlh1-Pms1 Endonuclease Active Site and an Exonuclease 1-Independent Mismatch Repair Pathway

Thu, 31 Oct 2013 04:00:00 +0100

by Catherine E. Smith, Marc L. Mendillo, Nikki Bowen, Hans Hombauer, Christopher S. Campbell, Arshad Desai, Christopher D. Putnam, Richard D. Kolodner Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC) is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR) caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A) that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasm...



Circulating gastrin concentrations in patients at increased risk of developing colorectal carcinoma

Mon, 21 Oct 2013 04:00:00 +0100

ConclusionConcentrations of gastrin precursors are increased in particular groups with an increased risk of developing CRC. (Source: Journal of Gastroenterology and Hepatology)



Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients

Thu, 03 Oct 2013 04:00:00 +0100

Conclusions: In conclusion, we classify five MLH1/MSH2 mutations as pathogenic, whereas four MLH1/MSH2/MSH6 mutations are classified as neutral. This study supports the notion that in silico prediction tools and mini-gene assays are important for the classification of intronic variants, and thereby crucial for the genetic counseling of patients and their family members. (Source: BMC Medical Genetics - Latest articles)

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Genes, Vol. 4, Pages 536-555: Copy Number Variation in Hereditary Non-Polyposis Colorectal Cancer

Thu, 26 Sep 2013 00:00:00 +0100

Hereditary non-polyposis colorectal cancer (HNPCC) is the commonest form of inherited colorectal cancer (CRC) predisposition and by definition describes families which conform to the Amsterdam Criteria or reiterations thereof. In ~50% of patients adhering to the Amsterdam criteria germline variants are identified in one of four DNA Mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Loss of function of any one of these genes results in a failure to repair DNA errors occurring during replication which can be most easily observed as DNA microsatellite instability (MSI)—a hallmark feature of this disease. The remaining 50% of patients without a genetic diagnosis of disease may harbour more cryptic changes within or adjacent to MLH1, MSH2, MSH6 or PMS2 or elsewhere in the genome. We used ...



Colorectal adenocarcinoma cancer in New Zealand in those under 25 years of age (1997–2007)

Mon, 16 Sep 2013 04:00:00 +0100

This study aimed to describe the population of young people in New Zealand diagnosed with colorectal cancer, their tumour characteristics, management and outcomes. MethodsA retrospective clinical study was conducted via review of medical records for all patients 25 years of age and under, diagnosed with colorectal adenocarcinoma in New Zealand between 1 January 1997 and 31 December 2007. ResultsFifty patients with colorectal adenocarcinoma were identified from the New Zealand Cancer Registry. Seven had a positive family history of colorectal cancer, while eight had predisposing factors (hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, ulcerative colitis, Crohn's disease, regional enteritis). The most common presenting symptoms were abdominal pain and weight loss. ...



Germline deletions in the EPCAM gene as a cause of Lynch syndrome -- literature review.

Mon, 12 Aug 2013 04:00:00 +0100

Authors: Tutlewska K, Lubinski J, Kurzawski G Abstract Lynch syndrome (clinically referred to as HNPCC -- Hereditary Non-Polyposis Colorectal Cancer) is a frequent, autosomal, dominantly-inherited cancer predisposition syndrome caused by various germline alterations that affect DNA mismatch repair genes, mainly MLH1 and MSH2. Patients inheriting this predisposition are susceptible to colorectal, endometrial and other extracolonic tumors. It has recently been shown that germline deletions of the last few exons of the EPCAM gene are involved in the etiology of Lynch syndrome. Such constitutional mutations lead to subsequent epigenetic silencing of a neighbouring gene, here, MSH2, causing Lynch syndrome. Thus, deletions of the last few exons of EPCAM constitute a distinct class of mut...



Survival of patients with Stage III colon cancer is improved in hereditary non‐polyposis colorectal cancer compared with sporadic cases. A Danish registry based study

Tue, 30 Jul 2013 04:00:00 +0100

ConclusionHNPCC patients with Stage III CC have a better OS compared with sporadic CC. No significant difference in OS was found within HNPCC subgroups. (Source: Colorectal Disease)



Hereditary Syndromes With Associated Renal Neoplasia: A Practical Guide to Histologic Recognition in Renal Tumor Resection Specimens

Mon, 01 Jul 2013 05:00:00 +0100

Many hereditary tumor syndromes are associated with neoplasms of the kidney. It is becoming increasingly well recognized that a given familial tumor syndrome may be very heterogenous in clinical appearance and that unrecognized patients may present initially for the treatment of a renal mass. It is therefore important for surgical pathologists to be aware of the specific gross and microscopic findings in the kidney that suggest a possible syndromic association. In this review, we detail the histologic features of syndromic-associated renal neoplasms, describe the presence of characteristic changes in the background renal parenchyma, and provide an update on associated extrarenal manifestations for each of the following syndromes: von Hippel-Lindau disease, hereditary papillary renal cell c...

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