A Better, Faster, Cancer Genetic Test?

BRCA harmful mutations identified with new test

/ Author:  / Reviewed by: Robert Carlson, M.D

(RxWiki News) A major risk factor for breast cancer is carrying a harmful mutation in the BRCA1 or BRCA2 genes. Finding out whether or not a BRCA gene alteration is harmful hasn’t been all that easy, though. That could be changing.

Researchers have developed a new test which appears to accurately predict the presence of harmful BRCA1 or BRCA2 mutations. This inexpensive test may become useful in identifying carriers at highest risk of developing breast cancer.

"If breast cancer runs in your family, get tested."

This small study was led by breast cancer specialist, Asher Y. Salmon, MD, at the Hadassah Hebrew University Medical Center in Jerusalem, Israel.

"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," Dr. Salmon said in a press release. "In many cases, the current sequencing tool identifies a mutation, but we do not know if the mutation is neutral [causes no harm] or harmful."

Harmful BRCA1 mutation increases a woman’s risk of developing either breast cancer and/or ovarian cancer. This mutation may also increase her chances of cervical, colon, pancreatic and uterine cancer. Harmful alterations in BRCA2 may be associated with higher risks of bile duct, gallbladder, pancreatic and stomach cancer, as well as melanoma.

According to Dr. Salmon, the latest scientific evidence suggests that BRCA genes with harmful mutations have a specific profile when they’re exposed to DNA-changing substances such as radiation.

To test this theory, researchers collected white blood cells from nine healthy women who had a mutated BRCA1 gene and eight healthy women with an altered BRCA2 gene. The cells were cultured and then exposed to radiation. These cells were then compared with treated white blood cells from 10 healthy women who didn’t not carry BRCA mutations.

Dr. Salmon and his team found that about 1,500 genes were expressed differently between carriers and non-carriers. This group was then narrowed down to 18 genes that were the most different in both groups.

The model was tested on blood samples from 40 carriers and 17 women who weren’t carriers.

This test accurately identified women with the harmful mutation 95 out of a 100 times. That means it had sensitivity of 95 percent. The test also had specificity – meaning it accurately identified patients who did not have the mutation – of 88 percent.

Dr. Salmon reported that the test is quick, inexpensive and has demonstrated accuracy in patients of different ethnicities. BRCA tests using DNA sequencing cost between $300 and $3,000 depending on how much of the gene is examined.

He concluded that this test may be particularly helpful in poorer areas where DNA sequencing isn’t available.

dailyRx News spoke with Adam Brufsky, MD, PhD, professor of medicine at the University of Pittsburgh. “Since it does not involve direct DNA sequencing, but rather tests for the effects of the lack of the BRCA gene product, it may be very useful at some point in the future in finding subtle mutations in BRCA1 and/or BRCA2 that direct DNA sequencing as currently done may not find,” Dr. Brufsky said.

Dr. Salmon and his team are planning studies in the United States and Europe to validate these findings in larger, more diverse populations.

This research was published January 22 in Cancer Prevention Research, a journal of the American Association for Cancer Research. Dr. Salmon has commercial research support from Micromedic, Israel, as does another author. Dr. Salmon has financial relationships with Novartis, Pfizer, and Johnson & Johnson. Another author has an ownership interest in the patent owned by Hadassah Medical Organization. No potential conflicts of interest were disclosed by the other authors.

Reviewed by: 
Review Date: 
January 20, 2013
Last Updated:
January 22, 2013