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

对临床定义的高级别浆液性卵巢癌亚群进行分子分析

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

Abstract

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.

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