PMID- 37400526 OWN - NLM STAT- MEDLINE DCOM- 20230705 LR - 20230706 IS - 2399-3642 (Electronic) IS - 2399-3642 (Linking) VI - 6 IP - 1 DP - 2023 Jul 3 TI - Genetic characterization of primary and metastatic high-grade serous ovarian cancer tumors reveals distinct features associated with survival. PG - 688 LID - 10.1038/s42003-023-05026-3 [doi] LID - 688 AB - High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and the majority of cases present with metastasis and late-stage disease. Over the last few decades, the overall survival for patients has not significantly improved, and there are limited targeted treatment options. We aimed to better characterize the distinctions between primary and metastatic tumors based on short- or long-term survival. We characterized 39 matched primary and metastatic tumors by whole exome and RNA sequencing. Of these, 23 were short-term (ST) survivors (overall survival (OS) < 3.5 years) and 16 were long-term (LT) survivors (OS > 5 years). We compared somatic mutations, copy number alterations, mutational burden, differential gene expression, immune cell infiltration, and gene fusion predictions between the primary and metastatic tumors and between ST and LT survivor cohorts. There were few differences in RNA expression between paired primary and metastatic tumors, but significant differences between the transcriptomes of LT and ST survivors in both their primary and metastatic tumors. These findings will improve the understanding of the genetic variation in HGSC that exist between patients with different prognoses and better inform treatments by identifying new targets for drug development. CI - (c) 2023. The Author(s). FAU - Kotnik, Emilee N AU - Kotnik EN AUID- ORCID: 0000-0002-9229-3378 AD - Division of Gynecologic Oncology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Center for Reproductive Health Sciences, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. FAU - Mullen, Mary M AU - Mullen MM AD - Division of Gynecologic Oncology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Center for Reproductive Health Sciences, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. FAU - Spies, Nicholas C AU - Spies NC AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Pathology and Immunology, Washington University in St. Louis, 660 S. Euclid Ave CB, 8118, St. Louis, MO, USA. FAU - Li, Tiandao AU - Li T AUID- ORCID: 0000-0003-1650-0555 AD - Department of Developmental Biology, Washington University in St. Louis, 660 S. Euclid Ave CB, 8103, St. Louis, MO, USA. FAU - Inkman, Matthew AU - Inkman M AUID- ORCID: 0000-0001-5490-2374 AD - Department of Radiation Oncology, Washington University in St. Louis, 660 S. Euclid Ave CB, 8224, St. Louis, MO, USA. FAU - Zhang, Jin AU - Zhang J AUID- ORCID: 0000-0002-9117-2793 AD - Department of Radiation Oncology, Washington University in St. Louis, 660 S. Euclid Ave CB, 8224, St. Louis, MO, USA. FAU - Martins-Rodrigues, Fernanda AU - Martins-Rodrigues F AUID- ORCID: 0000-0002-2140-0690 AD - Division of Oncology, Washington University in St. Louis, 660 S. Euclid Ave CB, 8069, St. Louis, MO, USA. FAU - Hagemann, Ian S AU - Hagemann IS AUID- ORCID: 0000-0002-3855-9745 AD - Division of Gynecologic Oncology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Center for Reproductive Health Sciences, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Pathology and Immunology, Washington University in St. Louis, 660 S. Euclid Ave CB, 8118, St. Louis, MO, USA. FAU - McCourt, Carolyn K AU - McCourt CK AD - Division of Gynecologic Oncology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Center for Reproductive Health Sciences, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. FAU - Thaker, Premal H AU - Thaker PH AD - Division of Gynecologic Oncology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Center for Reproductive Health Sciences, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. FAU - Hagemann, Andrea R AU - Hagemann AR AD - Division of Gynecologic Oncology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Center for Reproductive Health Sciences, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. FAU - Powell, Matthew A AU - Powell MA AD - Division of Gynecologic Oncology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Center for Reproductive Health Sciences, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. FAU - Mutch, David G AU - Mutch DG AD - Division of Gynecologic Oncology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Center for Reproductive Health Sciences, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. FAU - Khabele, Dineo AU - Khabele D AD - Division of Gynecologic Oncology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Center for Reproductive Health Sciences, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. FAU - Longmore, Gregory D AU - Longmore GD AUID- ORCID: 0000-0001-7568-8151 AD - Division of Oncology, Washington University in St. Louis, 660 S. Euclid Ave CB, 8069, St. Louis, MO, USA. AD - ICCE Institute, Washington University in St. Louis, 660 S. Euclid Ave CB, 8225, St. Louis, MO, USA. FAU - Mardis, Elaine R AU - Mardis ER AUID- ORCID: 0000-0002-5892-1553 AD - Institute for Genomic Medicine, Nationwide Children's Hospital, 575 Childrens Crossroad, Columbus, OH, USA. FAU - Maher, Christopher A AU - Maher CA AUID- ORCID: 0000-0002-9035-603X AD - Division of Oncology, Washington University in St. Louis, 660 S. Euclid Ave CB, 8069, St. Louis, MO, USA. AD - McDonnell Genome Institute, Washington University in St. Louis, 4444 Forest Park Avenue, CB 8501, St. Louis, MO, USA. AD - Department of Internal Medicine, Washington University in St. Louis, 660 S. Euclid Ave, MSC 8066-22-6602, St. Louis, MO, USA. AD - Department of Biomedical Engineering, Washington University in St. Louis, McKelvey School of Engineering, 1 Brookings Drive, St. Louis, MO, USA. FAU - Miller, Christopher A AU - Miller CA AD - Division of Oncology, Washington University in St. Louis, 660 S. Euclid Ave CB, 8069, St. Louis, MO, USA. FAU - Fuh, Katherine C AU - Fuh KC AUID- ORCID: 0000-0002-7693-2694 AD - Division of Gynecologic Oncology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. katherine.fuh@ucsf.edu. AD - Center for Reproductive Health Sciences, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. katherine.fuh@ucsf.edu. AD - Department of Obstetrics and Gynecology, Washington University in St. Louis, 660 S. Euclid Ave Mailstop, 8064, St. Louis, MO, USA. katherine.fuh@ucsf.edu. AD - Department of Obstetrics and Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA. katherine.fuh@ucsf.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230703 PL - England TA - Commun Biol JT - Communications biology JID - 101719179 SB - IM MH - Humans MH - Female MH - *Ovarian Neoplasms/pathology MH - Prognosis MH - DNA Copy Number Variations PMC - PMC10318066 COIS- The authors declare no competing interests. EDAT- 2023/07/04 01:05 MHDA- 2023/07/05 06:42 PMCR- 2023/07/03 CRDT- 2023/07/03 23:20 PHST- 2022/07/05 00:00 [received] PHST- 2023/06/07 00:00 [accepted] PHST- 2023/07/05 06:42 [medline] PHST- 2023/07/04 01:05 [pubmed] PHST- 2023/07/03 23:20 [entrez] PHST- 2023/07/03 00:00 [pmc-release] AID - 10.1038/s42003-023-05026-3 [pii] AID - 5026 [pii] AID - 10.1038/s42003-023-05026-3 [doi] PST - epublish SO - Commun Biol. 2023 Jul 3;6(1):688. doi: 10.1038/s42003-023-05026-3.