title: A636P testing in Ashkenazi Jews.
abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited colorectal cancer syndrome attributable to mutations in one of several DNA mismatch repair genes, most commonly MLH1 and MSH2 . In certain populations, founder mutations account for a substantial portion of HNPCC. In this report we summarize the literature and our personal experience testing for a specific founder mutation in the Ashkenazi Jewish population, MSH2*1906G > C , also known as A636P. Although rare in the general population, the A636P mutation is detected in up to 7% of Ashkenazi Jewish patients with early age-of-onset colorectal cancer, and may account for up to one third of HNPCC in the Ashkenazi Jewish population. In addition, we summarize our initial experience with a prospective A636P testing protocol aimed at Ashkenazi Jewish patients at high or intermediate risk for harboring the A636P mutation.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Guillem
authors.forename: Harvey G
authors.initials: HG
authors.lastname: Moore
authors.forename: Crystal
authors.initials: C
authors.lastname: Palmer
authors.forename: Emily
authors.initials: E
authors.lastname: Glogowski
authors.forename: Rob
authors.initials: R
authors.lastname: Finch
authors.forename: Khedoudja
authors.initials: K
authors.lastname: Nafa
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Markowitz
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Ellis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000483:Alleles; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology*; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D016019:Survival Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1