[Experience at Sheba Hospital in oncogenetic counseling and genetic testing of women with a high risk for breast and ovarian cancer].

There is inherited predisposition to breast and ovarian cancer in 5-10% of all women with these diseases. Germline mutations in BRCA1 and BRCA2 presumably account for most of the genetically susceptible individuals. We summarize 2 years of experience in counseling and testing for inherited predisposition to these cancers.

Common origin of the I1307K APC polymorphism in Ashkenazi and non-Ashkenazi Jews.

A common germline missense mutation within the APC gene, I1307K, has recently been described in Ashkenazi Jews. We detected this polymorphism in two non-Ashkenazi Jewish women using denaturing gradient gel electrophoresis (DGGE), and hypothesized that in Jewish individuals it might not be restricted to Ashkenazim, and actually reflect a common ancestral polymorphism. To test this notion we performed allelic pattern determination using APC-linked markers in these two women and in nine Ashkenazi carrier controls.

An identical novel mutation in BRCA1 and a common haplotype in familial ovarian cancer in non-Ashkenazi Jews.

Unique germline mutations in BRCA1 and BRCA2 account for inherited predisposition to breast and ovarian cancer in high-risk families. In Jewish high-risk individuals of Ashkenazi (east European) descent, three predominant mutations, 185delAG and 5382insC (BRCA1) and 6174delT (BRCA2), seem to account for a substantial portion of germline mutations, and two of these mutations (185delAG and 6174delT) are also found at about 1% each in the general Jewish-Ashkenazi population. We identified a novel BRCA1 mutation in two Jewish-non-Ashkenazi families with ovarian cancer: a thymidine to guanidine alteration at position 3053, resulting in substitution of tyrosine at codon 1017 for a stop codon (Tyr1017Ter).

The 185delAG BRCA1 mutation originated before the dispersion of Jews in the diaspora and is not limited to Ashkenazim.

The 185delAG mutation in BRCA1 is detected in Ashkenazi Jews both in familial breast and ovarian cancer and in the general population. All tested Ashkenazi mutation carriers share the same allelic pattern at the BRCA1 locus. Our previous study showed that this 'Ashkenazi' mutation also occurs in Iraqi Jews with a similar allelic pattern.