Conference Proceedings
Abstract IA02: DNA repair gene promoter methylation patterns adapt and influence PARP inhibitor response
Kasenija Nesic, Rachel M Hurley, Cordelia McGehee, Olga Kondrashova, Maria I Harrell, Giada V Zapparoli, Ashan Musafer, Ming E Wong, John Weroha, Xiaonan Hou, Hu Li, Vivian Negron, Kevin Peterson, Paula Schneider, Elizabeth M Swisher, Melissa Southey, Alexander Dobrovic, Matthew Wakefield, Scott H Kaufmann, Clare L Scott
Clinical Cancer Research | American Association for Cancer Research (AACR) | Published : 2020
Abstract
Abstract PARP inhibitor (PARPi) resistance in high-grade serous ovarian carcinoma (HGSOC) can be acquired as a result of restored homologous recombination (HR) due to secondary or reversion mutations in HR genes, such as BRCA1, BRCA2, and RAD51C, or due to loss of BRCA1 promoter methylation (meBRCA1). We have demonstrated that homozygous meBRCA1 can be lost or reverted to heterozygous methylation following treatment with platinum-based chemotherapy, resulting in HR-competent PARPi-resistant tumors. RAD51C promoter methylation (meRAD51C) is detected in approximately 2% of HGSOC cases and, as with meBRCA1, is associated with gene silencing and HR deficiency. We are exploring PAR..
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