A group of researchers has recently identified several new mutations that are associated with inherited risk for breast cancer. These new mutations are not identified by the current genetic screening tests for BRCA1 and BRCA2. The study by University of Washington researchers published March 22, 2006 in the Journal of the American Medical Association, reports new mutations occurring on the BRCA1 and BRCA2 genes as well as mutations occurring on two other genes called CHEK2 and TP53.

In the study, DNA was collected from 300 patients who were from high-risk families and had breast or ovarian cancer but had received negative results from the standard BRCA test. The researchers ran additional tests on this DNA using various techniques including one known as a multiple ligation-dependent probe amplification (MLPA) that allows detection of mutations due to large rearrangements in the DNA. In 35 of the 300 patients, the researchers found previously undetected mutations in the BRCA1 and BRCA2 genes.

In response, the U.S. company that offers the BRCA analysis, a patented test, said on its web site that it was “actively developing a test to detect all such large rearrangements and anticipates that the test will be available for patients with severe family history before the end of the year.” Another commercial test incorporating MLPA technology is available in Europe, reported the Wall Street Journal, but not in the U.S.

The study also identified 17 mutations on other cancer-associated genes – CHEK1 and TP53. The commercial BCRA tests do not look at these other genes. The researchers pointed out that testing for these other mutations can be obtained through a number of for-profit and not-for-profit laboratories in the U.S.

A person with a strong family history of breast or ovarian cancer (with at least three affected relatives) and a negative result from the standard BRCA test should recognize that the test has limitations. It may not detect the gene defect that is contributing to cancer in that family.

Sources
S1
Walsh T, Casadei S, Coats KH, et al. Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. J Amer Med Assoc. 2006;295(12):1379-88.

S2
Myriad Genetic Laboratories. Spectrum of mutations in BRCA1 and BRCA2 in families with severe family history for breast/ovarian cancer (featured article on company Web site). On the Internet: http://www.myriadtests.com/provider/feature.htm. Accessed 9 Jun 2006.

S3
Burton TM. Test for breast-cancer risk could miss mark. Wall Street Journal. 22 Mar 2006, p. D4.