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Researchers identify mechanism of cancer caused by loss of BRCA1 and BRCA2 gene function
Date:4/28/2014

y, when we studied cells lacking BRCA1 or BRCA2, we found that the frequency of aberrant HR events triggered at Tus/Ter-stalled replication forks had actually increased compared to normal cells. We knew at this point that we had discovered a new and important process by which BRCA gene loss promotes cancer."

The discovery provides a promising bridge between basic science and the clinic, says Scully. "Sometimes a genetic sequencing test reveals a mutation in BRCA1 or BRCA2 that has not been definitively associated with cancer," he explains. Often described as "Variants of Uncertain Significance" (VUS), these mutations are not found in high enough frequency in healthy women or in women with breast or ovarian cancers to allow the specific BRCA1 or BRCA2 mutations to be reliably classified as high risk or low risk. This is an important issue since a woman with a known high-risk BRCA gene mutation may elect to undergo potentially lifesaving prophylactic mastectomy or oophorectomy, as Scully further explains.

"There is a growing appreciation that careful measurement of the HR functions of BRCA1 and BRCA2 VUS mutants might help to classify them into high risk or low risk groups," he notes. "It would be gratifying if our system could contribute new information to help ongoing efforts to classify these VUS mutants."

Furthermore, he adds, understanding the mechanisms that regulate HR at stalled replication forks might hold additional promise for the development of novel cancer therapeutics. "If we could use this tool to help develop new cancer therapies, it would be a grand slam," says Scully. "This new system might also be useful in genome editing, which is considered groundbreaking technology used for the development of new gene therapies."


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Contact: Bonnie Prescott
bprescot@bidcm.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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