This method has been applied to chromosome bands 17q12-q21, a region that includes a gene (BRCA1) involved in early onset familial breast and ovarian cancer.
The breast cancer susceptibility gene BRCA1 has been cloned and a second susceptibility gene, BRCA2, chromosomally mapped; will most breast and ovarian cancer turn out to be familial?
A proximal region affected by LOH is located in a 22-cM region defined by D17S73 and NME1 and thus is similar in location to the region thought to contain the BRCA1 gene associated with familial breast and breast/ovarian cancer.
Because BRCA1 mutations also increase women's risk for ovarian cancer, we asked whether Jewish women are at higher risk for familial ovarian cancer than non-Jewish women.
The comparison of clinicopathological features with the obtained data revealed that LOH at the BRCA1 locus was significantly correlated with features specific for familial BRCA1 tumors and with absence of hormone receptors.
The tumor suppressor gene BRCA1 on chromosome 17q21 has been characterized and shown to be mutated in patients with familial breast and ovarian cancer.
Women with a BRCA1 mutation (n = 12) and relatives without the familial mutation (n = 10) were compared to controls (i.e., healthy women without family history of breast or ovarian cancer; n = 17).
Pedigree information from the mutation carriers was used to estimate penetrance and the proportion of familial risk of breast cancer due to BRCA1 and BRCA2.
Commercially available BRCA1 antibodies lack the specificity required to identify the BRCA1 protein and thus are not useful for establishing differences between familial and sporadic breast tumours, or between BRCA1 associated and non-BRCA1 associated breast tumours.
Of those samples previously determined to overexpress the HER2 protein, HER2 amplification was detected in one of three tumours from BRCA1 mutation carriers and in 13 of 17 tumours of the age matched non-familial cases.
Despite the relatively high prevalence of ovarian cancer (1% of American women will develop this disease in their lifetime) and recent developments in its molecular genetic understanding (several proto-oncogenes, such as AKT2 and cKRAS, and tumor suppressor genes, such as BRCA1 and BRCA2, have been implicated), little is known about the presence of ovarian tumors and cancer in women already diagnosed with other familial multiple tumor syndromes.
Germ-line mutations in BRCA1 account for the majority of familial breast and ovarian cancer cases and development of cancer in individuals who carry such mutations requires somatic inactivation of the normal allele.