Somatic mutations in mismatch repair genes in sporadic gastric carcinomas are not a cause but a consequence of the mutator phenotype

Cancer Genetics and Cytogenetics
Mafalda PintoRobert M W Hofstra

Abstract

In hereditary nonpolyposis colorectal cancer (HNPCC), patients' mismatch repair (MMR) gene mutations cause MMR deficiency, leading to microsatellite instability (MSI-H). MSI-H is also found in a substantial fraction of sporadic gastric carcinomas (SGC), mainly due to MLH1 promoter hypermethylation, although somatic mutations in MMR genes have been described. We aimed to investigate which MMR defects are present in SGC. Twenty-nine MSI-H SGC investigated previously for MLH1 promoter hypermethylation were screened for somatic mutations in MLH1, MSH2, MSH6, MLH3, and MBD4 by denaturing gradient gel electrophoresis and sequencing. Five truncating mutations (three in MSH6, one in MLH3, and one in MBD4) and one missense mutation (MLH1) were identified. Of these, three truncating mutations were in MSI-H cases that lack MLH1 hypermethylation. As all truncating mutations were found in the coding poly-A tracts, it seems likely that they result from the MSI phenotype rather than cause it. In summary, somatic mutations in MMR genes are rare in SGC and do not explain the development of these tumors reflecting, rather than causing, the mutator phenotype. Other MMR genes are probably involved in MSI-H gastric cancer without MLH1 hypermethylat...Continue Reading

References

Feb 20, 1995·International Journal of Cancer. Journal International Du Cancer·R SerucaM Sobrinho-Simões
Nov 1, 1995·Human Molecular Genetics·A L BørresenR D Kolodner
Mar 1, 1997·Genes, Chromosomes & Cancer·L D KowalskiP J Goodfellow
Jun 9, 1998·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J D HaydenI G Martin
Jul 8, 1999·The American Journal of Pathology·K C HallingS M Powell
Mar 21, 2001·Human Molecular Genetics·P Peltomäki

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Citations

Aug 7, 2009·Human Genetics·Anya N MilneG J A Offerhaus
Jan 20, 2009·Familial Cancer·Corrado PedrazzaniFranco Roviello
Nov 19, 2008·Seminars in Diagnostic Pathology·Fátima CarneiroRaquel Seruca
Jun 10, 2010·International Journal of Cancer. Journal International Du Cancer·Marina LeiteRaquel Seruca
Apr 2, 2016·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Namrata SetiaGregory Y Lauwers
May 28, 2010·International Journal of Surgical Pathology·Fátima Carneiro
Jun 2, 2017·World Journal of Gastrointestinal Oncology·Silvio Ken GarattiniGiuseppe Aprile
Dec 4, 2014·World Journal of Gastroenterology : WJG·Sérgia VelhoRaquel Seruca
Jun 9, 2018·International Journal of Molecular Sciences·Lara AlessandriniVincenzo Canzonieri

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