Israeli researchers, led by Dr. Asher Salmon, then Senior Oncologist at the Hadassah Medical Center, developed a blood test that reveals it is possible to predict the presence of harmful BRCA1 and BRCA2 mutations in otherwise healthy women using a novel technology called gene expression profiling.

Women with a mutation in their BRCA1 or BRCA2 gene have a significantly increased risk for developing breast or ovarian cancer. For many of those at risk, the disease may develop at an early age.

“This novel technology aims to provide a layer of information regarding the cell functionality aspect of BRCA mutations that could greatly enhance the doctor’s ability to identify high-risk carriers,” explains Dr. Salmon. With gene expression profiling, researchers can search for genes that have the potential to distinguish healthy BRCA1 and BRCA2 mutation carriers from noncarriers.

The only other test available to detect these mutations is full gene sequencing; however, as Dr. Salmon points out, it is “expensive, time consuming and, in many cases, lacks clear and decisive information for making a clinical decision.” Many times, it cannot be determined if the mutation is neutral or harmful.

New evidence has revealed that cells with a mutation in one of the two copies of the BRCA1 or BRCA2 genes display a distinct gene expression profile when they are exposed to elements that cause DNA damage, such as radiation. Knowing this, Dr. Salmon and his team collected white blood cells from the blood samples donated by 17 healthy women who had a mutated BRCA gene. They cultured the cells and then exposed them to radiation. Next, they extracted the RNA from these cells and compared it to the RNA from identically treated white blood cells from 10 healthy women who did not carry the BRCA gene. The researchers found that approximately 1500 genes were differentially expressed between carriers and noncarriers. They then narrowed this list to 18 genes that were the most significantly differentiated between the two groups of women.

They validated their results with another two groups of women—40 carriers of the BRCA mutation and 17 noncarriers. Their validation model showed a sensitivity of 95 percent.

According to Dr. Salmon, the test can reveal whether a patient carries a harmful mutation regardless of the specificity of the mutation. “In societies where gene sequencing is not feasible, this test can substitute for it with a very high accuracy rate,” Dr. Salmon relates.

Hadasit, Hadassah’s technology transfer arm, identified the economic and scientific potential of this new development, protected it with a patent, and commercialized it to Biogene, a daughter company of Micromedic, which is working on developing a diagnostic kit based on the research.

The Israeli research team–which included Prof. Tamar Peretz, Director of Hadassah’s Sharrett Institute of Oncology, and physicians from Tel Hashomer Hospital, Bar Ilan University, Barzilai Medical Center, and Ariel University Center–reported their findings in Cancer Prevention Research, a journal of the American Association for Cancer Research. “In summary,” the researchers write, “our study provides insight into the biologic effect of heterozygous mutations in BRCA1 and BRCA2 genes in response to ionizing irradiation-induced DNA damage. We also suggest a set of 18 genes that can serve as a prediction and screening tool for BRCA1 or BRCA2 mutational carriers by using easily obtained lymphocytes.”

(See “Determination of Molecular Markers for BRCA1 and BRCA2 Heterozygosity Using Gene Expression Profiling,” Cancer Prev Res; 6(2); 1–9. ©2013 AACR.)