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Molecular Analysis of Clinically Defined Subsets of High-Grade Serous Ovarian Cancer

Authors: Lee, Sanghoon; Zhao, Li; Rojas, Christine; Bateman, Nicholas W.; Yao, Hui; Lara, Olivia D.; Celestino, Joseph; Morgan, Margaret B.; Nguyen, Tri V.; Conrads, Kelly A.; Rangel, Kelly M.; Dood, Robert L.; Hajek, Richard A.; Fawcett, Gloria L.; Chu, Randy A.; Wilson, Katlin; Loffredo, Jeremy L.; Viollet, Coralie; Jazaeri, Amir A.; Dalgard, Clifton L.; Mao, Xizeng; Song, Xingzhi; Zhou, Ming; Hood, Brian L.; Banskota, Nirad; Wilkerson, Matthew D.; Te, Jerez; Soltis, Anthony R.; Roman, Kristin; Dunn, Andrew; Cordover, David; Eterovic, Agda Karina; Liu, Jinsong; Burks, Jared K.; Baggerly, Keith A.; Fleming, Nicole D.; Lu, Karen H.; Westin, Shannon N.; Coleman, Robert L.; Mills, Gordon B.; Casablanca, Yovanni; Zhang, Jianhua; Conrads, Thomas P.; Maxwell, George L.; Futreal, P. Andrew; Sood, Anil K.

Online: https://linkinghub.elsevier.com/retrieve/pii/S2211124720303922

Issue: Cell Rep. 2020 Apr 14;31(2):107502.


The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC), which is the most lethal gynecologic malignancy, is not well understood. Here, we perform comprehensive multi-platform omics analyses, including integrated analysis, and immune monitoring on primary and metastatic sites from highly clinically annotated HGSC samples based on a laparoscopic triage algorithm from patients who underwent complete gross resection (R0) or received neoadjuvant chemotherapy (NACT) with excellent or poor response. We identify significant distinct molecular abnormalities and cellular changes and immune cell repertoire alterations between the groups, including a higher rate of NF1 copy number loss, and reduced chromothripsis-like patterns, higher levels of strong-binding neoantigens, and a higher number of infiltrated T cells in the R0 versus the NACT groups.

Keywords: R0 resection; copy number; genomics; immune monitoring; multi-omics; mutation; neoadjuvant chemotherapy; ovarian cancer; proteome; transcriptome.