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BROCA sequencing approach evaluates all 24 genes implicated in breast cancer
Date:10/24/2013

nts in all 24 genes implicated in breast cancer.

The researchers used BROCA to test 2,285 members of 743 families with at least three relatives with breast or ovarian cancer. Each of those families included at least one woman with breast cancer who had received normal results from complete commercial genetic testing for BRCA1 and BRCA2. The commercial tests were based on both Sanger sequencing and supplementary testing for large genomic rearrangements in both genes.

Of the 743 families, 26% (191) were resolved by BROCA. The 191 resolved families were found to harbor 149 different inherited, damaging mutations in 18 distinct genes.

Of the 191 resolved families, 35% (66) carried inherited, damaging mutations in BRCA1 or BRCA2 that were not detected by commercial sequencing. The scientists explained that the BRCA mutations were not detected by commercial testing for one of two reasons. In some families, the patient who was tested had normal sequences of BRCA1 and BRCA2, but her relatives with breast cancer carried a mutation in one of those genes. In other families, both the patient who was tested and her relatives carried a BRCA1 or BRCA2 mutation of a type not reported by commercial testing.

In the remaining families resolved by BROCA, 65% (125) carried inherited, damaging mutations in genes other than BRCA1 or BRCA2 that also have been associated with breast cancer. The researchers found that 18 different genes harbored cancer-predisposing mutations in those 125 families, but each affected person carried a mutation in only one gene.

Carriers of mutations in some of the genes were at significantly increased risk of ovarian cancer for women and increased risk of breast cancer in men as well as in women.

Comprehensive testing is rapidly becoming more widespread. "It is important to determine more precisely the risks associated with damaging mutations in each of these genes so as to incorporate them most effecti
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Contact: Cathy Yarbrough
press@ashg.org
858-243-1814
American Society of Human Genetics
Source:Eurekalert

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