Dissecting the Impact of Mutational Processes on Therapeutic Response in Ovarian Cancer
Abstract
High grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy and while treatment with PARP inhibitors has shown some promise for patients with BRCA1/2 mutations these mutations remain an imperfect predictor for response. Our team has established structural variant-associated mutational processes for patient risk stratification: homologous recombination deficient (HRD) tumors, either associated with BRCA1 mutation-linked duplications (HRD-Dup) or BRCA2 mutation-linked interstitial deletions (HRD-Del), have a better prognosis than homologous recombination proficient tumors, including CDK-12 associated tandem duplications (TD) and foldback inversion (FBI) bearing tumors. Our hypothesis is that these distinct mutational processes confer differential evolutionary capacity on the malignant cells and impact treatment response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1197684
Entities
People
- Sohrab Shah
Organizations
- Memorial Sloan Kettering Cancer Center