A636P testing in Ashkenazi Jews.
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.
Guillem
Jose G
JG
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Moore
Harvey G
HG
Palmer
Crystal
C
Glogowski
Emily
E
Finch
Rob
R
Nafa
Khedoudja
K
Markowitz
Arnold J
AJ
Offit
Kenneth
K
Ellis
Nathan A
NA
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
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1