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Mutant Gene That Ups Risk for Ovarian Cancer May Aid Survival
Date:10/11/2011

o 44 percent of women with BRCA1 mutation and 25 percent of women without either mutation.

The three-year progression-free survival rate, or the time during which the tumor did not grow, was 44 percent for BRCA2 women, 22 percent for BRCA1 women and 16 percent for women with neither mutation.

Women with BRCA2 also responded better to platinum-based chemotherapy, the standard treatment for ovarian cancer.

All women with the BRCA2 mutation saw their tumor shrink in response to chemo, compared to 80 percent for women with BRCA1 and 82 percent of women with the typical form of the gene.

After treatment ended, women with BRCA2 went an average of 18 months without the tumor re-growing, compared to 12.5 months for women with BRCA1 and 11.7 months for women without either mutation, the investigators found.

To determine why women with BRCA2 respond better to chemotherapy, researchers conducted whole-exome sequencing using blood and tumor tissue samples. The exome is the portion of the genome that contains genes that code for proteins.

The BRCA gene is involved with repairing DNA errors. The BRCA mutations are believed to make women more susceptible to certain cancers because their ability to fix DNA damage is impaired, Yang said.

Platinum-based chemotherapy also causes a large amount of DNA damage.

The exome sequencing revealed that women with BRCA2 had more DNA mutations that had occurred throughout their lifetimes (as opposed to being inherited at birth) than women with BRCA1.

In women with BRCA2, the ability to repair DNA damage is impaired not just in healthy cells, but in the cancerous tissues as well.

In women with BRCA2, because the tumor cells are not able to repair themselves against the assault of the platinum, that means the tumor itself is less likely to thrive as the cells die off, Yang said.

"We have shown that only the BRCA2 is associated with better chemotherapy response, better progression
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