The founder Ashkenazi Jewish mutations in the MSH2 and MSH6 genes in Israeli patients with gastric and pancreatic cancer.
The genetic basis for gastric and pancreatic cancer is largely undetermined. These cancers are overrepresented in hereditary non polyposis colon cancer (HNPCC), inherited cancer syndrome attributed to germline mutations primarily in the MSH2, MLH1 and MSH6 genes. Among Ashkenazi Jewish HNPCC cases, recurring mutations in the MSH2 (1906G>C; A636P) and MSH6 (c.3984_3987dupGTCA; c.3959_3962delCAAG) genes can be detected. The MSH6*c.3984_3987dupGTCA mutation was recently detected in an Ashkenazi family with inherited gastric cancer. We hypothesized that it may be possible to detect the recurring MSH2 and MSH6 mutations in Jewish individuals with familial and sporadic gastric and pancreatic cancer. To test this notion, we genotyped 143 unrelated Jewish Israeli patients with gastric (n = 23) and pancreatic (n = 120) cancer. The majority of cases (100/143-70%) were Ashkenazi Jews, and 10% (n = 16)--of mixed Ashkenazi-non Ashkenazi Jewish ancestry, and most participants (n = 96-67.1%) had a positive family history of cancer. Genotyping the MSH2*A636P mutation was performed by PCR followed by restriction enzyme digest, and the MSH6*c.3984_3987dupGTCA and c.3959_3962delCAAG mutations were detected by fragment size analysis by capillary electrophoresis and sequencing. None of the participants harbored any of the genotyped MSH2 or MSH6 mutations. We conclude that the recurring Ashkenazi MSH2 and MSH6 mutations contribute little if any to sporadic and familial gastric and pancreatic cases in Israeli patients.
The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, The Chaim Sheba Medical Center, 52621, Tel HaShomer, Israel.
Yael
Y
Laitman
Liron
L
Herskovitz
Talia
T
Golan
Bella
B
Kaufman
Shani Shimon
SS
Paluch
Eitan
E
Friedman
D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010375:Pedigree; D013274:Stomach Neoplasms / Q000235:genetics*
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein