Molecular assessment of colorectal cancer through Lynch syndrome screening

Since 2017, the National Institute for Health and Care Excellence (NICE) has recommended molecular testing of all patients with newly diagnosed colorectal cancer (CRC) to identify those with suspected Lynch syndrome who should be referred to clinical genetics for germline testing. The pathway involves firstly determining the mismatch repair (MMR) expression status by immunohistochemistry (IHC) or performing microsatellite instability testing. This may be followed by BRAF V600E mutation testing and then MLH1 promoter hypermethylation analysis depending on the result.
Source: Diagnostic Histopathology - Category: Pathology Authors: Tags: Mini-symposium: Gastrointestinal/Hepato-Pancreato-Biliary Pathology Source Type: research

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This study aims at examining the frequency, patterns and molecular etiologies of such inter-tumoral MMR discordances. We analyzed a cohort of 2159 colorectal cancer (CRC) patients collected over a 5-year period and found that 1.3% of the patients (27/2159) had  ≥ 2 primary CRCs, and 25.9% of the patients with ≥ 2 primary CRCs (7/27) exhibited inter-tumoral MMR discordance. We then combined the seven MMR-discordant CRC patients with three additional MMR-discordant GIT carcinoma patients and evaluated their discordant patterns and associated mol ecular abnormalities. The 10 patients consiste...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
AbstractThere has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as aBRCA2 pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39  years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, L...
Source: International Cancer Conference Journal - Category: Cancer & Oncology Source Type: research
ConclusionsOur data is consistent with the results from other studies including US Hispanics, where approximately 10% of Hispanic individuals with colorectal cancer have microsatellite instability. Our results support universal tumor-based screening for LS among Hispanics in accordance with National Comprehensive Cancer Network guidelines.
Source: Journal of Racial and Ethnic Health Disparities - Category: International Medicine & Public Health Source Type: research
ConclusionsUpdated risk assessment and genetic counseling with a discussion of the benefits and limitations of germline and somatic genetic testing, is essential as the understanding of UMMRD and genetic testing recommendations for this population evolve.
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
AbstractMicrosatellite instability (MSI) is an effective biomarker for diagnosing Lynch syndrome (LS) and predicting the responsiveness of cancer therapy. MSI testing is conventionally performed by capillary electrophoresis, and MSI status is judged by visual assessment of allele size change. Here, we attempted to develop a quantitative evaluation model of MSI using next-generation sequencing (NGS). Microsatellite markers were analyzed in tumor and non-tumor tissues of colorectal cancer patients by NGS after a single multiplex polymerase chain reaction amplification. The read counts corresponding to microsatellite loci len...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
by Neil A. J. Ryan, Raymond McMahon, Simon Tobi, Tristan Snowsill, Shona Esquibel, Andrew J. Wallace, Sancha Bunstone, Naomi Bowers, Ioana E. Mosneag, Sarah J. Kitson, Helena O ’Flynn, Neal C. Ramchander, Vanitha N. Sivalingam, Ian M. Frayling, James Bolton, Rhona J. McVey, D. Gareth Evans, Emma J. Crosbie BackgroundLynch syndrome (LS) predisposes to endometrial cancer (EC), colorectal cancer, and other cancers through inherited pathogenic variants affecting mismatch-repair (MMR) genes. Diagnosing LS in women with EC can reduce subsequent cancer mortality through colonoscopic surveillance and aspirin chemoprevention;...
Source: PLoS Medicine - Category: Internal Medicine Authors: Source Type: research
In conclusion, LLS should be classified as a mixed entity, containing cases of LS, other hereditary cancer syndromes, and sporadic CRC. The high risks of CRC and extra-CRCs, which were found in this study, suggest tailored management policy and surveillance should be formulated based on individual and family risk. The surveillance regimen can be based on the presence of confirmed pathogenic/likely pathogenic germline variant(s) and family history.
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Abstract Persons with Lynch syndrome (LS - carrying a pathogenic mutation in a DNA mismatch repair gene) have an increased colorectal cancer (CRC) and endometrial cancer (EC) risk. A high reported variability in cancer risk suggests the existence of factors that modify cancer risk for LS. We aimed to investigate the association between height and CRC and EC for persons with LS using two large studies. Information of 1,213 men and 1,636 women with LS from the Colon Cancer Family Registry (1998-2007) and the GEOLynch cohort study (2006-2017) was harmonized. We used weighted Cox proportional hazard regression models ...
Source: Am J Epidemiol - Category: Epidemiology Authors: Tags: Am J Epidemiol Source Type: research
Authors: Peltomäki P, Olkinuora A, Nieminen TT Abstract INTRODUCTION: Up to one third of colorectal cancers show familial clustering and 5% are hereditary single-gene disorders. Hereditary non-polyposis colorectal cancer comprises DNA mismatch repair-deficient and -proficient subsets, represented by Lynch syndrome (LS) and familial colorectal cancer type X (FCCTX), respectively. Accurate knowledge of molecular etiology and genotype-phenotype correlations are critical for tailored cancer prevention and treatment. AREAS COVERED: The authors highlight advances in the molecular dissection of hereditary non-pol...
Source: Expert Review of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Expert Rev Gastroenterol Hepatol Source Type: research
It has been>15 years since universal microsatellite instability (MSI) or mismatch repair (MMR) testing has been recommend for all cases of colorectal carcinoma.1 MSI/MMR testing is a proven prognostic marker and can help identify patients with possible hereditary cancers (Lynch syndrome).2,3 More recently, checkpoint inhibition therapy has been found to be effective in tumors that demonstrate MSI, making MSI/MMR testing a pan-cancer therapeutic biomarker.4 Given its importance, multiple organizations, including the American Society of Clinical Oncology, Association for Molecular Pathology, College of American Pathologis...
Source: Gastroenterology - Category: Gastroenterology Authors: Tags: Editorial Source Type: research
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