A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.

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 TW, Chiu HS, Lefever S, Liu L, MacKenzie K, Orsulic S, Roszik J, Shelley CS, Song Q, Vellano CP, Wentzensen N, Cancer Genome Atlas Research Network, Weinstein JN, Mills GB, Levine DA, Akbani R
Cancer Cell. 2018 33 (4): 690-705.e9

PMID: 29622464 · PMCID: PMC5959730 · DOI:10.1016/j.ccell.2018.03.014

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.

Copyright © 2018 Elsevier Inc. All rights reserved.

MeSH Terms (15)

Breast Neoplasms Databases, Genetic DNA Copy Number Variations Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Regulatory Networks Genetic Predisposition to Disease Genital Neoplasms, Female Humans Mutation Organ Specificity Prognosis Receptors, Estrogen RNA, Long Noncoding

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