Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 (BRCA1/2) confer a greatly increased lifetime risk for breast and ovarian cancers. In patients with these inherited mutations, only one of the two inherited BRCA1/2 copies is broken so the single normal functioning BRCA1/2 protein must provide the DNA repair and chromosome maintenance functions that are essential for life. In contrast to healthy tissue, tumors in patients with BRCA1/2 mutations exhibit loss of the normal copy of BRCA1 or BRCA2. This loss is considered an early, pivotal step in cancer development. Although there have been studies of BRCA1 and BRCA2 loss in tumors, DNA in these tumors is highly unstable, with frequent rearrangements of large DNA segments, making it difficult to understand the events that led to BRCA1 or BRCA2 loss in normal precursor cells before they became cancerous. In this study, the Jasin laboratory plans to develop approaches to detect loss of the functional copy of BRCA1 and BRCA2 in “normal” cells derived from human breast and ovary, to detect rare events that can have enormous consequences in cancer development. The researchers’ ultimate goal is to identify ways to suppress the loss of the functional copy and thereby suppress cancer development.
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