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A comprehensive pan-cancer molecular study of gynecologic and breast cancers

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Title: A comprehensive pan-cancer molecular study of gynecologic and breast cancers
Authors: Berger, AC
Korkut, A
Kanchi, RS
Hegde, AM
Lenoir, W
Liu, W
Liu, Y
Fan, H
Shen, H
Ravikumar, V
Rao, A
Schultz, A
Li, X
Sumazin, P
Williams, C
Mestdagh, P
Gunaratne, PH
Yau, C
Bowlby, R
Robertson, AG
Tiezzi, DG
Wang, C
Cherniack, AD
Godwin, AK
Kuderer, NM
Rader, JS
Zuna, RE
Sood, AK
Lazar, AJ
Ojesina, AI
Adebamowo, C
Adebamowo, SN
Baggerly, KA
Chen, T-W
Chiu, H-S
Lefever, S
Liu, L
MacKenzie, K
Orsulic, S
Roszik, J
Shelley, CS
Song, Q
Vellano, CP
Wentzensen, N
Weinstein, JN
Mills, GB
Levine, DA
Akbani, R
Item Type: Journal Article
Abstract: We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.
Issue Date: 9-Apr-2018
Date of Acceptance: 12-Mar-2018
URI: http://hdl.handle.net/10044/1/71239
DOI: https://doi.org/10.1016/j.ccell.2018.03.014
ISSN: 1535-6108
Publisher: Elsevier
Start Page: 690
End Page: 705.e9
Journal / Book Title: Cancer Cell
Volume: 33
Issue: 4
Copyright Statement: © 2018 Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
MUTATIONAL SIGNATURES
CLASS DISCOVERY
ACCURATE
MICROARRAY
GENERATION
LANDSCAPE
REVEALS
PFKFB3
QUANTIFICATION
IDENTIFICATION
TCGA
The Cancer Genome Atlas
breast cancer
cervical cancer
gynecologic cancer
omics
ovarian cancer
pan-gynecologic
uterine cancer
uterine carcinosarcoma
Breast Neoplasms
DNA Copy Number Variations
Databases, Genetic
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Genetic Predisposition to Disease
Genital Neoplasms, Female
Humans
Mutation
Organ Specificity
Prognosis
RNA, Long Noncoding
Receptors, Estrogen
Cancer Genome Atlas Research Network
Humans
Breast Neoplasms
Genital Neoplasms, Female
Genetic Predisposition to Disease
Receptors, Estrogen
Prognosis
Gene Expression Profiling
Organ Specificity
Gene Expression Regulation, Neoplastic
Mutation
Databases, Genetic
Female
Gene Regulatory Networks
DNA Copy Number Variations
RNA, Long Noncoding
Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
MUTATIONAL SIGNATURES
CLASS DISCOVERY
ACCURATE
MICROARRAY
GENERATION
LANDSCAPE
REVEALS
PFKFB3
QUANTIFICATION
IDENTIFICATION
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
1109 Neurosciences
Publication Status: Published
Open Access location: https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30119-3
Online Publication Date: 2018-04-02
Appears in Collections:Department of Surgery and Cancer