학술논문
Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer
Document Type
Article
Author
Burdett, Nikki L.; Willis, Madelynne O.; Alsop, Kathryn; Hunt, Allison L.; Pandey, Ahwan; Hamilton, Phineas T.; Abulez, Tamara; Liu, Xuan; Hoang, Therese; Craig, Stuart; Fereday, Sian; Hendley, Joy; Garsed, Dale W.; Milne, Katy; Kalaria, Shreena; Marshall, Ashley; Hood, Brian L.; Wilson, Katlin N.; Conrads, Kelly A.; Pishas, Kathleen I.; Ananda, Sumitra; Scott, Clare L.; Antill, Yoland; McNally, Orla; Mileshkin, Linda; Hamilton, Anne; Au-Yeung, George; Devereux, Lisa; Thorne, Heather; Bild, Andrea; Bateman, Nicholas W.; Maxwell, G. Larry; Chang, Jeffrey T.; Conrads, Thomas P.; Nelson, Brad H.; Bowtell, David D. L.; Christie, Elizabeth L.
Source
Nature Genetics; March 2023, Vol. 55 Issue: 3 p437-450, 14p
Subject
Language
ISSN
10614036; 15461718
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.