Molecular Subclasses of Clear Cell Ovarian Carcinoma and Their Impact on Disease Behavior and Outcomes.

Autor:	Bolton KL; Washington University School of Medicine, St. Louis, Missouri., Chen D; Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania., Corona de la Fuente R; Cedars-Sinai Medical Center, Los Angeles, California., Fu Z; University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania., Murali R; Memorial Sloan-Kettering Cancer Center, New York, New York., Köbel M; The University of Calgary, Calgary, Alberta, Canada., Tazi Y; Memorial Sloan-Kettering Cancer Center, New York, New York., Cunningham JM; Mayo Clinic, Rochester, Minnesota., Chan ICC; Washington University School of Medicine, St. Louis, Missouri., Wiley BJ; Washington University School of Medicine, St. Louis, Missouri., Moukarzel LA; Memorial Sloan-Kettering Cancer Center, New York, New York., Winham SJ; Mayo Clinic, Rochester, Minnesota., Armasu SM; Mayo Clinic, Rochester, Minnesota., Lester J; David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, California., Elishaev E; University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania., Laslavic A; University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania., Kennedy CJ; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia., Piskorz A; University of Cambridge, Cambridge, United Kingdom., Sekowska M; University of Cambridge, Cambridge, United Kingdom., Brand AH; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.; The University of Sydney, Sydney, New South Wales, Australia., Chiew YE; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia., Pharoah P; University of Cambridge, Cambridge, United Kingdom., Elias KM; Brigham and Women's Hospital, Boston, Massachusetts., Drapkin R; University of Pennsylvania, Philadelphia, Pennsylvania., Churchman M; University of Edinburgh, Edinburgh, United Kingdom., Gourley C; University of Edinburgh, Edinburgh, United Kingdom., DeFazio A; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.; The University of Sydney, Sydney, New South Wales, Australia.; The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, New South Wales, Australia., Karlan B; David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, California., Brenton JD; University of Cambridge, Cambridge, United Kingdom., Weigelt B; Memorial Sloan-Kettering Cancer Center, New York, New York., Anglesio MS; University of British Columbia, Vancouver, British Columbia, Canada., Huntsman D; University of British Columbia, Vancouver, British Columbia, Canada., Gayther S; Cedars-Sinai Medical Center, Los Angeles, California., Konner J; Memorial Sloan-Kettering Cancer Center, New York, New York., Modugno F; University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania., Lawrenson K; Cedars-Sinai Medical Center, Los Angeles, California., Goode EL; Mayo Clinic, Rochester, Minnesota., Papaemmanuil E; Memorial Sloan-Kettering Cancer Center, New York, New York.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Nov 14; Vol. 28 (22), pp. 4947-4956.
DOI:	10.1158/1078-0432.CCR-21-3817
Abstrakt:	Purpose: To identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes. Experimental Design: 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. Results: 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. Conclusions: 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. (©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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