Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer
- Author(s)
- Burdett, NL; Willis, MO; Alsop, K; Hunt, AL; Pandey, A; Hamilton, PT; Abulez, T; Liu, X; Hoang, T; Craig, S; Fereday, S; Hendley, J; Garsed, DW; Milne, K; Kalaria, S; Marshall, A; Hood, BL; Wilson, KN; Conrads, KA; Pishas, KI; Ananda, S; Scott, CL; Antill, Y; McNally, O; Mileshkin, L; Hamilton, A; Au-Yeung, G; Devereux, L; Thorne, H; Bild, A; Bateman, NW; Maxwell, GL; Chang, JT; Conrads, TP; Nelson, BH; Bowtell, DDL; Christie, EL;
- Journal Title
- Nature Genetics
- Publication Type
- Research article
- Abstract
- High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multiomics approach to interrogate molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means. We also observed frequent whole-genome duplication and global changes in immune composition with evidence of immune escape. This analysis highlights diverse evolutionary changes within HGSC that evade therapy and ultimately overwhelm individual patients.
- Publisher
- Nature Portfolio
- Keywords
- Humans; Female; *Ovarian Neoplasms/genetics; Multiomics; Carcinoma, Ovarian Epithelial; Homologous Recombination/genetics; *Cystadenocarcinoma, Serous/genetics
- Department(s)
- Laboratory Research; Medical Oncology; Laboratory Research; Medical Oncology
- PubMed ID
- 36849657
- Publisher's Version
- https://doi.org/10.1038/s41588-023-01320-2
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-04-13 02:29:11
Last Modified: 2023-04-13 05:40:48