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New tests urged for breast cancer gene mutations.(Gynecology)
Patients at high risk for breast cancer are not getting the full story from the genetic tests now being carried out in the United States, according to a study by Tom Walsh, Ph.D, and his associates.
Genetic testing is recommended for women with family histories of breast and ovarian cancer that suggest they may have inherited BRCA1 or BRCA2 gene mutations. To determine the frequency and type of cancer-predisposing gene mutations that are undetected by the most commonly used genetic tests, Dr. Walsh and his associates enrolled 300 representatives of cancer-afflicted families, or "probands" (JAMA 2006;295:1379-88).
"The clinical dilemma is what to offer to women with a high probability of carrying a mutation in BRCA1 and BRCA2 but with negative commercial test results," the researchers wrote. The U.S. probands comprised 291 women with invasive breast cancer, three males with invasive breast cancer, and six women with ovarian cancer; 95% were of European ancestry. All participants had family histories of four or more cases of breast and ovarian cancer, and all had negative (wild-type) genetic test results for BRCA1 and BRCA2.
Participants were tested for complete "inherited rearrangements" of BRCA1 and BRCA2--and for other major breast cancer susceptibility genes, including CHEK2 (a cell cycle regulator), PTEN, and TP53--using multiplex ligation-dependent probe amplification (MLPA), a testing method available in Europe through a commercial firm in Amsterdam. The test is not available in the United States, and the researchers disclosed no financial interest in any company involved in this study.
"We believe that for families testing negative (wild type) for BRCA1 and BRCA2 by conventional sequencing, MLPA ... is the current best choice," Dr. Walsh and associates wrote.
Of the 300 probands with negative (wild-type) BRCA1 and BRCA2 commercial test results, 12% carried "cancer-predisposing genomic deletions or duplications in one of these genes," the investigators reported. Additionally, 4% had inherited CHEK2 mutations, and 1% carried TP53 mutations. Of these probands, 52 (17%) carried inherited mutations in BRCA1, BRCA2, CHEK2, and ...
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Source: HighBeam Research, New tests urged for breast cancer gene mutations.(Gynecology)