PMID- 31340883 OWN - NLM STAT- MEDLINE DCOM- 20191024 LR - 20200901 IS - 1095-6859 (Electronic) IS - 0090-8258 (Print) IS - 0090-8258 (Linking) VI - 154 IP - 3 DP - 2019 Sep TI - Molecular profiling and molecular classification of endometrioid ovarian carcinomas. PG - 516-523 LID - S0090-8258(19)31398-8 [pii] LID - 10.1016/j.ygyno.2019.07.012 [doi] AB - OBJECTIVE: Endometrioid ovarian carcinomas (EOCs) comprise 5-10% of all ovarian cancers and commonly co-occur with synchronous endometrioid endometrial cancer (EEC). We sought to examine the molecular characteristics of pure EOCs in patients without concomitant EEC. METHODS: EOCs and matched normal samples were subjected to massively parallel sequencing targeting 341-468 cancer-related genes (n = 8) or whole-genome sequencing (n = 28). Mutational frequencies of EOCs were compared to those of high-grade serous ovarian cancers (HGSOCs; n = 224) and EECs (n = 186) from The Cancer Genome Atlas, and synchronous EOCs (n = 23). RESULTS: EOCs were heterogeneous, frequently harboring KRAS, PIK3CA, PTEN, CTNNB1, ARID1A and TP53 mutations. EOCs were distinct from HGSOCs at the mutational level, less frequently harboring TP53 but more frequently displaying KRAS, PIK3CA, PIK3R1, PTEN and CTNNB1 mutations. Compared to synchronous EOCs and pure EECs, pure EOCs less frequently harbored PTEN, PIK3R1 and ARID1A mutations. Akin to EECs, EOCs could be stratified into the four molecular subtypes: 3% POLE (ultramutated), 19% MSI (hypermutated), 17% copy-number high (serous-like) and 61% copy-number low (endometrioid). In addition to microsatellite instability, a subset of EOCs harbored potentially targetable mutations, including AKT1 and ERBB2 hotspot mutations. EOCs of MSI (hypermutated) subtype uniformly displayed a good outcome. CONCLUSIONS: EOCs are heterogeneous at the genomic level and harbor targetable genetic alterations. Despite the similarities in the repertoire of somatic mutations between pure EOCs, synchronous EOCs and EECs, the frequencies of mutations affecting known driver genes differ. Further studies are required to define the impact of the molecular subtypes on the outcome and treatment of EOC patients. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Cybulska, Paulina AU - Cybulska P AD - Department of Surgery, Gynecology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Paula, Arnaud Da Cruz AU - Paula ADC AD - Department of Surgery, Gynecology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Tseng, Jill AU - Tseng J AD - Department of Surgery, Gynecology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Leitao, Mario M Jr AU - Leitao MM Jr AD - Department of Surgery, Gynecology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Bashashati, Ali AU - Bashashati A AD - Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada. FAU - Huntsman, David G AU - Huntsman DG AD - Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada. FAU - Nazeran, Tayyebeh M AU - Nazeran TM AD - Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada. FAU - Aghajanian, Carol AU - Aghajanian C AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Abu-Rustum, Nadeem R AU - Abu-Rustum NR AD - Department of Surgery, Gynecology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - DeLair, Deborah F AU - DeLair DF AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Shah, Sohrab P AU - Shah SP AD - Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada; Department of Epidemiology & Biostatistics, Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Weigelt, Britta AU - Weigelt B AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: weigeltb@mskc.org. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190721 PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Endometrioid/*classification/genetics/pathology MH - Carcinoma, Ovarian Epithelial/*classification/genetics/pathology MH - Cystadenocarcinoma, Serous/classification/genetics/pathology MH - DNA Mutational Analysis MH - Female MH - Humans MH - Microsatellite Instability MH - Middle Aged MH - Neoplasm Staging MH - Ovarian Neoplasms/*classification/genetics/pathology MH - Progression-Free Survival MH - Retrospective Studies PMC - PMC6736779 MID - NIHMS1535885 OTO - NOTNLM OT - Endometrioid ovarian cancer OT - Heterogeneity OT - Massively parallel sequencing OT - Molecular subtypes OT - Somatic mutations COIS- CONFLICT OF INTEREST M.M. Leitao Jr is an ad hoc speaker for Intuitive Surgical, Inc. C. Aghajanian reports personal fees from Tesaro, Immunogen, Clovis, Mateon Therapeutics, Cerulean Pharma, and grants from Clovis, Genentech, AbbVie and Astra Zeneca, outside the submitted work. N.R. Abu-Rustum reports grants from Stryker/Novadaq, Olympus and GRAIL paid to the institution, outside the submitted work. S.P. Shah is founder, shareholder and consultant of Contextual Genomics Inc., outside the submitted work. The remaining authors have no conflicts of interest to declare. EDAT- 2019/07/26 06:00 MHDA- 2019/10/28 06:00 PMCR- 2020/09/01 CRDT- 2019/07/26 06:00 PHST- 2019/04/19 00:00 [received] PHST- 2019/07/09 00:00 [revised] PHST- 2019/07/10 00:00 [accepted] PHST- 2019/07/26 06:00 [pubmed] PHST- 2019/10/28 06:00 [medline] PHST- 2019/07/26 06:00 [entrez] PHST- 2020/09/01 00:00 [pmc-release] AID - S0090-8258(19)31398-8 [pii] AID - 10.1016/j.ygyno.2019.07.012 [doi] PST - ppublish SO - Gynecol Oncol. 2019 Sep;154(3):516-523. doi: 10.1016/j.ygyno.2019.07.012. Epub 2019 Jul 21.