New gene test predicts presence of high-risk BRCA mutations

A new multiple gene expression profile test appears to be a useful screening tool for identifying women with a harmful BRCA1 or BRCA2 gene mutation.

With approximately 5% of all breast cancers attributable to an inherited mutation in one of two cancer susceptibility genes, BRCA1 and BRCA2, Asher Y. Salmon, MD, and colleagues searched for genes that have the potential to distinguish healthy BRCA1 and BRCA2 mutation carriers from noncarriers based on differences in expression profiling. Salmon, a breast cancer specialist at the Hadassah Hebrew University Medical Center in Jerusalem, Israel, and his fellow researchers described their findings in Cancer Prevention Research, a journal of the American Association for Cancer Research (AACR).

The investigators collected white blood cells from nine healthy women with a mutated BRCA1 gene and eight healthy women with a mutated BRCA2 gene. The cells were cultured and exposed to radiation. Salmon explained in an accompanying statement from the AACR that emerging evidence has revealed cells with a mutation in one of the two copies of the BRCA1 or BRCA2 genes have a distinct gene expression profile when exposed to radiation or other causes of DNA damage.

After this treatment, the total RNA from these cells was extracted and compared with the total RNA from identically treated white blood cells from 10 healthy, noncarrier women.

Of approximately 1,500 genes expressed differently between carriers and noncarriers, Salmon's team found the 18 that were most significantly differentiated. A validation study revealed that this 18-gene model had 95% sensitivity and 88% specificity in predicting the presence of harmful BRCA1 or BRCA2 mutations in otherwise healthy women carrying the mutations.

“The current tool for mutation detection is gene sequencing, which is expensive, time-consuming, and, in many cases, lacking clear and decisive clinical decision-making information,” pointed out Salmon in the AACR statement. “In many cases, the current sequencing tool identifies a mutation, but we do not know if the mutation is neutral or harmful.”

The new test, however, is affordable and quick, and can portray whether a person carries a harmful mutation regardless of ethnic origin or specific mutation, said Salmon. The investigators are launching a large validation study to analyze the efficacy of the test in heterogeneous populations.

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