journal contribution
posted on 2023-04-01, 00:08 authored by Kelly L. Bolton, Denise Chen, Rosario Corona de la Fuente, Zhuxuan Fu, Rajmohan Murali, Martin Köbel, Yanis Tazi, Julie M. Cunningham, Irenaeus C.C. Chan, Brian J. Wiley, Lea A. Moukarzel, Stacey J. Winham, Sebastian M. Armasu, Jenny Lester, Esther Elishaev, Angela Laslavic, Catherine J. Kennedy, Anna Piskorz, Magdalena Sekowska, Alison H. Brand, Yoke-Eng Chiew, Paul Pharoah, Kevin M. Elias, Ronny Drapkin, Michael Churchman, Charlie Gourley, Anna DeFazio, Beth Karlan, James D. Brenton, Britta Weigelt, Michael S. Anglesio, David Huntsman, Simon Gayther, Jason Konner, Francesmary Modugno, Kate Lawrenson, Ellen L. Goode, Elli Papaemmanuil Supplementary Figure from Molecular Subclasses of Clear Cell Ovarian Carcinoma and Their Impact on Disease Behavior and Outcomes
Funding
National Cancer Institute (NCI)
United States Department of Health and Human Services
Find out more...Cycle for Survival
Breast Cancer Research Foundation (BCRF)
Damon Runyon Cancer Research Foundation (DRCRF)
American Society of Hematology (ASH)
Evans Medical Foundation (Evans Foundation)
Michael Smith Foundation for Health Research (MSFHR)
BC Cancer Foundation
Cancer Research UK (CRUK)
NIHR Cambridge Biomedical Research Centre (NIHR Cambridge BRC)
History
ARTICLE ABSTRACT
To identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes.
We profiled 421 primary CCOCs that passed quality control using a targeted deep sequencing panel of 163 putative CCOC driver genes and whole transcriptome sequencing of 211 of these tumors. Molecularly defined subgroups were identified and tested for association with clinical characteristics and overall survival.
We detected a putative somatic driver mutation in at least one candidate gene in 95% (401/421) of CCOC tumors including ARID1A (in 49% of tumors), PIK3CA (49%), TERT (20%), and TP53 (16%). Clustering of cancer driver mutations and RNA expression converged upon two distinct subclasses of CCOC. The first was dominated by ARID1A-mutated tumors with enriched expression of canonical CCOC genes and markers of platinum resistance; the second was largely comprised of tumors with TP53 mutations and enriched for the expression of genes involved in extracellular matrix organization and mesenchymal differentiation. Compared with the ARID1A-mutated group, women with TP53-mutated tumors were more likely to have advanced-stage disease, no antecedent history of endometriosis, and poorer survival, driven by their advanced stage at presentation. In women with ARID1A-mutated tumors, there was a trend toward a lower rate of response to first-line platinum-based therapy.
Our study suggests that CCOC consists of two distinct molecular subclasses with distinct clinical presentation and outcomes, with potential relevance to both traditional and experimental therapy responsiveness.See related commentary by Lheureux, p. 4838
