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

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

doi:10.1016/j.celrep.2020.03.066

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

Cell Rep. 2020 Apr 14;31(2):107502. doi: 10.1016/j.celrep.2020.03.066.

Authors

Sanghoon Lee¹, Li Zhao², Christine Rojas³, Nicholas W Bateman⁴, Hui Yao⁵, Olivia D Lara⁶, Joseph Celestino⁶, Margaret B Morgan⁷, Tri V Nguyen⁶, Kelly A Conrads⁴, Kelly M Rangel⁶, Robert L Dood⁶, Richard A Hajek⁶, Gloria L Fawcett⁷, Randy A Chu⁷, Katlin Wilson⁴, Jeremy L Loffredo⁴, Coralie Viollet⁸, Amir A Jazaeri⁶, Clifton L Dalgard⁹, Xizeng Mao², Xingzhi Song², Ming Zhou³, Brian L Hood⁴, Nirad Banskota⁴, Matthew D Wilkerson¹⁰, Jerez Te¹⁰, Anthony R Soltis⁸, Kristin Roman¹¹, Andrew Dunn¹¹, David Cordover¹¹, Agda Karina Eterovic⁷, Jinsong Liu¹², Jared K Burks¹³, Keith A Baggerly⁵, Nicole D Fleming⁶, Karen H Lu⁶, Shannon N Westin⁶, Robert L Coleman⁶, Gordon B Mills¹, Yovanni Casablanca¹⁴, Jianhua Zhang², Thomas P Conrads³, George L Maxwell³, P Andrew Futreal², Anil K Sood¹⁵

Affiliations

¹ Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
² Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Women's Health Integrated Research Center at Inova Health System, Women's Service Line, Inova Fairfax Medical Campus, Falls Church, VA, USA; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
⁴ Women's Health Integrated Research Center at Inova Health System, Women's Service Line, Inova Fairfax Medical Campus, Falls Church, VA, USA; Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
⁵ Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
⁹ The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹⁰ The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
¹¹ Akoya Biosciences, Marlborough, MA, USA.
¹² Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹³ Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁴ Gynecologic Cancer Center of Excellence, Department of Obstetrics and Gynecology, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA.
¹⁵ Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: asood@mdanderson.org.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Cystadenocarcinoma, Serous / pathology*
Female
Gene Expression Profiling / methods
Genomics / methods
Humans
Metabolomics / methods
Middle Aged
Ovarian Neoplasms / genetics
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology*

Abstract

Publication types

MeSH terms

Grants and funding