In most families affected by HBOC, genetic linkage to a polymorphism on chromosome 17q21 has been found (84-86). Named BRCA1, this gene was finally cloned in 1994 (87), and one year later, BRCA2 was isolated at chromosome 13q12 (88) (Table 3). Approximately, 90% of familial ovarian cancers are caused by germline mutations in the BRCA1 gene, and most of the remaining are because of alterations in BRCA2 (89). These genes are transmitted in an autosomal dominant fashion to offspring.

Although, BRCA1 and BRCA2 appear to be important in the development of familial ovarian cancer, significantly they do not appear to affect sporadic tumors. Mutations in

Table 3

Genes Involved in Familial Ovarian Cancer Syndromes



Percent of ovarian cancer cases

Percent of ovarian cancer cases in each syndrome

Hereditary breast and ovarian cancer syndrome

BRCA1 17q21 4.1

BRCA2 13p12 3.3

Hereditary nonpolyposis colorectal cancer

DNA mismatch - 2.9

repair genes:

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