Rosana Risques, PhD
University of Washington
2017 Pape Family Pilot Study Award
Characterization of TP53 mutations in BRCA carcinogenesis
Women with inherited mutations in the BRCA1 and BRCA2 genes have a greatly increased risk of developing high-grade serous ovarian cancer (HGSOC). This type of cancer starts as a lesion in the fallopian tube, and these lesions almost always contain cells with a mutation in a gene called TP53, which is commonly mutated in many types of cancers. Dr. Risques and colleagues recently reported the important discovery that mutations in TP53 are common in normal tissue as well and that these mutations are more abundant in older women with mutations in the BRCA1 and BRCA2 genes. They concluded that mutations in TP53 accumulate in normal tissue during the aging process, and that their increased frequency might be associated with the development of cancer. Based on these findings, Dr. Risques hypothesizes that women with BRCA1 and BRCA2 mutations have more TP53 mutations in their fallopian tubes than other women. Remarkably, Dr. Risques has also been able to find these TP53 mutations without invasive surgery to study the fallopian tubes. She can find the frequency of TP53 mutations in a patient from collecting blood samples. In this study, Dr. Risques will determine if women with the BRCA1 and BRCA2 mutations carry more TP53 mutations in their blood, and whether this correlates with greater risk of developing ovarian cancer. If this proves true, sampling TP53 mutations in the blood could be an extremely easy, non-invasive way to determine a patient’s risk of developing ovarian cancer.