Recurrent and founder mutations in the PMS2 gene.

Clinical Genetics
J TomsicAlbert de la Chapelle

Abstract

Germline mutations in PMS2 are associated with Lynch syndrome (LS), the most common known cause of hereditary colorectal cancer. Mutation detection in PMS2 has been difficult due to the presence of several pseudogenes, but a custom-designed long-range PCR strategy now allows adequate mutation detection. Many mutations are unique. However, some mutations are observed repeatedly across individuals not known to be related due to the mutation being either recurrent, arising multiple times de novo at hot spots for mutations, or of founder origin, having occurred once in an ancestor. Previously, we observed 36 distinct mutations in a sample of 61 independently ascertained Caucasian probands of mixed European background with PMS2 mutations. Eleven of these mutations were detected in more than one individual not known to be related and of these, six were detected more than twice. These six mutations accounted for 31 (51%) ostensibly unrelated probands. Here, we performed genotyping and haplotype analysis in four mutations observed in multiple probands and found two (c.137G>T and exon 10 deletion) to be founder mutations and one (c.903G>T) a probable founder. One (c.1A>G) could not be evaluated for founder mutation status. We discuss po...Continue Reading

References

Nov 1, 1995·Nature Medicine·M Nyström-LahtiB Vogelstein
May 3, 2000·American Journal of Epidemiology·A Ashley-KochR S Olney
Sep 9, 2000·Journal of Medical Genetics·D C DesaiA de La Chapelle
Mar 7, 2003·The New England Journal of Medicine·Henry T Lynch, Albert de la Chapelle
Oct 24, 2003·American Journal of Human Genetics·Matthew Stephens, Peter Donnelly
Feb 12, 2004·JAMA : the Journal of the American Medical Association·Henry T LynchAlbert de la Chapelle
Feb 19, 2004·Journal of the National Cancer Institute·Asad UmarSudhir Srivastava
May 6, 2005·The New England Journal of Medicine·Heather HampelAlbert de la Chapelle
May 12, 2005·Gastroenterology·Kaspar TruningerGiancarlo Marra
Aug 9, 2005·Gastroenterology·Heather HampelAlbert de la Chapelle
Jan 20, 2006·The New England Journal of Medicine·Kathleen M SchmelerKaren H Lu
Apr 19, 2006·Human Mutation·Mark ClendenningAlbert de la Chapelle
Apr 25, 2007·British Journal of Cancer·L I H OverbeekM J L Ligtenberg
Nov 6, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Polly A NewcombUNKNOWN Colon Cancer Family Registry
Jan 8, 2008·Journal of Medical Genetics·M ClendenningA de la Chapelle
Apr 3, 2008·Cancer Research·Mark ClendenningAlbert de la Chapelle
Jul 8, 2008·Gastroenterology·Leigha SenterAlbert de la Chapelle
Sep 24, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Heather HampelAlbert de la Chapelle
Jan 7, 2009·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Glenn E PalomakiStephen N Thibodeau
Jan 22, 2009·European Journal of Human Genetics : EJHG·Laura GiuntiMaurizio Genuardi
Sep 2, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Heikki J JärvinenJukka-Pekka Mecklin
Dec 24, 2009·Journal of the National Cancer Institute·Laura BagliettoMark A Jenkins
Mar 6, 2010·Human Mutation·Cecily P VaughnWade S Samowitz
Sep 23, 2010·Cancer Research·Ester BorràsGabriel Capellá
Mar 8, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Johanna C HerkertRolf H Sijmons
May 28, 2011·Human Mutation·Cecily P VaughnJeffrey J Swensen
Jun 4, 2011·Journal of Medical Genetics·Aung Ko WinNoralane M Lindor
Jun 15, 2011·International Journal of Cancer. Journal International Du Cancer·Jerneja TomsicAlbert de la Chapelle

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Citations

Jul 11, 2013·Clinical Genetics·A J Brea-FernándezC Ruiz-Ponte
May 18, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Carin R EspenschiedHeather Hampel
Aug 12, 2014·World Journal of Gastroenterology : WJG·Laura Valle
Jan 21, 2020·International Journal of Cancer. Journal International Du Cancer·Hua MengYuntao Xie
Jan 30, 2020·Journal of Medical Genetics·Qing WangUNKNOWN French Consortium of Oncogenetic laboratories for colorectal cancers, Unicancer Cancer Genetic Group (GGC)

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