Loss of heterozygosity in the region including the BRCA1 gene on 17q in colon cancer.

Colon cancer has been proved to be an excellent model to identify and to study the different genetic alterations taking part in its development. BRCA1, a susceptibility gene for breast cancer, has been identified. Evidence of a significant risk for colon cancer in BRCA1-linked families has been reported. We undertook the present study to investigate the possible relation of BRCA1 and other genes on chromosome 17q21 to colon cancer. Eighty-five tumors were examined for loss of heterozygosity at seven microsatellite loci spanning the 17q21 region. Loss of heterozygosity was present in 39 (49%) of the 79 informative cases, with at least one marker. Two loci, D17S855 and D17S579, showed higher rates of allelic loss (16% and 22%, respectively) than the remaining markers. Tumors on the right side of the colon exhibited allelic loss more frequently than those on the left side. Our data suggest that BRCA1 and other genes in the 17q21 region may play an important role in the development of colon cancer.

Detection of BRCA1 gene mutations in families with breast cancer patients and their healthy relatives.

Eighty-three families with two or more cases of breast and ovarian cancer were selected to evaluate the prevalence rate of BRCA1 gene mutations, and identify healthy carriers. Blood samples from patients and healthy relatives were obtained. Haplotype study of the 17q21 region using 7 polymorphic markers was performed. Mutational analysis of the coding exons of the BRCA1 gene was performed by the PCR-SSCP method and direct sequencing. We detected germline mutations (frameshift and missense) in 6 families (9.1%). Combining haplotype analysis and PCR-SSCP screening, 18 (15%) healthy female carriers were identified. The prevalence rate of germline BRCA1 gene mutations among our families with breast cancer syndrome is low, and relatives having the same haplotype for the 17q21 region as mutation-carrying patients usually display the same genomic sequence as the patients.

Germ-line BRCA1 mutations in women with sporadic breast cancer: clinical correlations.

PURPOSE: Sporadic nonhereditary breast cancer is recognized as the most common form of this malignancy. Presence of germ-line mutations in the BRCA1 gene of these tumors is an infrequent event. We undertook the present study to evaluate the prevalence of germ-line mutations in patients diagnosed with sporadic breast cancer, and to delimit the clinical spectrum of this subgroup of patients with germ-line mutations and their differences with respect to patients with no evidence of BRCA1 gene mutations. METHODS: We studied 105 patients diagnosed with breast cancer, selected from among our living patients; those with carcinoma-in-situ and those with a definite family history of breast or ovarian cancer were excluded. Genomic DNA, obtained from peripheral-blood lymphocytes, was studied for BRCA1 mutations by polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. Fourteen clinicopathologic parameters were analyzed in each patient. RESULTS: Six (5.7%) frameshift mutations that corresponded to truncating proteins and three missense mutations, the functional meaning of which remains speculative, were identified. The patients with germ-line mutations were found to have a more advanced age at diagnosis, as well as a longer median survival (51 months). CONCLUSION: Women with sporadic breast cancer of late onset may display a significant incidence of germline BRCA1 mutations, which occur at a rate not previously determined in this group of patients. The presence of variations in the sequence of the BRCA1 gene could influence the longer survival observed in these patients.