Abstract B39: Molecular diagnostics strategy to identify hereditary non-polyposis colorectal cancer patients

• Published in: Clinical cancer research Vol. 16; no. 7_Supplement; p. B39
• Main Authors: Kostina, Olga, Rebane, Egle, Anderson, Wally, Kask, Martin, Valkna, Andres
• Format: Journal Article
• Language: English
• Published: 01.04.2010
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.TCME10-B39

Abstract Introduction: Hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch syndrome, is an autosomal dominantly inherited syndrome predisposing to the early development of cancers of colon, rectum, endometrial, small bowel and urinary tract and accounts for ∼5% of all colon cancer cases. Molecular investigations have shown that most HNPCC families are associated with constitutional mutations in a class of genes (called MLH1, MSH2, MSH6, PMS2 and probably others) involved in DNA mismatch repair. MLH1 and MSH2 genes account for approximately 90% of HNPCC families identified germline mutations. Most of these mutations are point mutations and small insertions or deletions. The large genomic deletions in MMR genes and germline epimutations in MLH1 explain a proportion of point mutation-negative families suspected of Lynch syndrome. At the same time the methylation in promoter of MLH1 gene in colon tissue frequently causes MLH1 protein loss in sporadic tumors. The aim of the study is to characterize the mismatch repair gene mutations of Estonian hereditary non-polyposis colorectal cancer families and to improve the screening strategy. Methods: A systematic analysis of 75 unrelated patients from suspected HNPCC families in Estonia was performed by immunohistochemistry, microsatellite instability, and gene mutation and methylation detection. Results. The study is still continuing. Systematic and comprehensive analysis of samples from 75 HNPCC-suspected patients is proceeding using various methods. Conclusion: Based on traditional molecular genetics, combined with epigenetics, multiple detection methods can accurately diagnose HNPCC. As the results of the study, the precise molecular diagnostic scheme for diagnosing HNPCC will be worked out for clinical use in Estonia. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B39