Recurrent germline mutations in BRCA... [Breast Cancer Res Treat. 2012] - PubMed - NCBI
Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in Israel.
Abstract
The spectrum of germline mutations among Jewish non Ashkenazi high risk breast/ovarian cancer
families includes a few predominant mutations in BRCA1 (185delAG and
Tyr978X) and BRCA2 (8765delAG). A few additional recurring mutations
[A1708E, 981delAT, C61G (BRCA1) R2336P, and IVS2 + 1G > A (BRCA2)]
have been reported in Jewish non Ashkenazi families. The 4153delA*BRCA1
C61G*BRCA1 and the 4075delGT*BRCA2 has been reported to recur in
Russian/Polish non Jews and Ashkenazim, respectively. The rate of these
recurring mutations has not been reported in Israeli high risk families.
Genotyping for these recurring mutations by restriction enzyme digest
and sequencing method was applied to high risk, predominantly cancer
affected, unrelated Israeli individuals of Ashkenazi (n = 827), non
Ashkenazi (n = 2,777), non Jewish Caucasians (n = 193), and 395 of mixed
ethnicity. Jewish participants included 827 Ashkenazi, 804 Balkans, 847
North Africans, 234 Yemenites, and 892 Asians (Iraq and Iran). Age at
diagnosis of breast cancer (median ± SD) (n = 2,484) was 47.2 ± 9.6 for all women participants. Males (n = 236) were also included, of whom 24 had breast cancer and 35 had pancreatic cancer.
Overall, 8/282 (2.8%) of the Balkan cases carried the BRCA1*A1708E
mutation, 4/180 (2.2%) the R2336P mutation, and 0/270 the
IVS2 + 1G > A BRCA2 mutations, respectively. Of North Africans, 7/264
(2.65%) carried the BRCA1*981delAT mutation. The BRCA1*C61G mutation
was detected in 3/269 Ashkenazi, non Ashkenazi, and non Jewish Russians;
the BRCA1*Tyr978X mutation was detected in 23/3220 individuals of non
Ashkenazi origin, exclusively of Asian ethnicity (23/892, 2.6% of the
Asians tested). The BRCA1*4153delA mutation was noted in 2/285 non
Jewish Caucasians, and none of the Ashkenazim (n = 500) carried the
BRCA2*4075delGT mutation. Jewish high risk families of North African,
Asian, and Balkan descent should be screened for the 981delAT, Tyr978X,
A1708E BRCA1, and the R2336P BRCA2 mutations, respectively.
