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

Cancer Genome Atlas Research Network

doi:10.1016/j.ccell.2018.03.014

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

Cancer Genome Atlas Research Network

Research output: Contribution to journal › Article › peer-review

497 Citations (Scopus)

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.

Original language	English
Pages (from-to)	690-705.e9
Journal	Cancer cell
Volume	33
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2018.03.014
Publication status	Published - 9 Apr 2018
Externally published	Yes

Keywords

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

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10.1016/j.ccell.2018.03.014

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@article{59a2429892d44e9089f125feec37f961,

title = "A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers",

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.",

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

author = "\{Cancer Genome Atlas Research Network\} and Berger, \{Ashton C\} and Anil Korkut and Kanchi, \{Rupa S\} and Hegde, \{Apurva M\} and Walter Lenoir and Wenbin Liu and Yuexin Liu and Huihui Fan and Hui Shen and Visweswaran Ravikumar and Arvind Rao and Andre Schultz and Xubin Li and Pavel Sumazin and Cecilia Williams and Pieter Mestdagh and Gunaratne, \{Preethi H\} and Christina Yau and Reanne Bowlby and Robertson, \{A Gordon\} and Tiezzi, \{Daniel G\} and Chen Wang and Cherniack, \{Andrew D\} and Godwin, \{Andrew K\} and Kuderer, \{Nicole M\} and Rader, \{Janet S\} and Zuna, \{Rosemary E\} and Sood, \{Anil K\} and Lazar, \{Alexander J\} and Ojesina, \{Akinyemi I\} and Clement Adebamowo and Adebamowo, \{Sally N\} and Baggerly, \{Keith A\} and Ting-Wen Chen and Hua-Sheng Chiu and Steve Lefever and Liang Liu and Karen MacKenzie and Sandra Orsulic and Jason Roszik and Shelley, \{Carl Simon\} and Qianqian Song and Vellano, \{Christopher P\} and Nicolas Wentzensen and Weinstein, \{John N\} and Mills, \{Gordon B\} and Levine, \{Douglas A\} and Rehan Akbani",

year = "2018",

month = apr,

day = "9",

doi = "10.1016/j.ccell.2018.03.014",

language = "English",

volume = "33",

pages = "690--705.e9",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "4",

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T1 - A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

AU - Cancer Genome Atlas Research Network

AU - Berger, Ashton C

AU - Korkut, Anil

AU - Kanchi, Rupa S

AU - Hegde, Apurva M

AU - Lenoir, Walter

AU - Liu, Wenbin

AU - Liu, Yuexin

AU - Fan, Huihui

AU - Shen, Hui

AU - Ravikumar, Visweswaran

AU - Rao, Arvind

AU - Schultz, Andre

AU - Li, Xubin

AU - Sumazin, Pavel

AU - Williams, Cecilia

AU - Mestdagh, Pieter

AU - Gunaratne, Preethi H

AU - Yau, Christina

AU - Bowlby, Reanne

AU - Robertson, A Gordon

AU - Tiezzi, Daniel G

AU - Wang, Chen

AU - Cherniack, Andrew D

AU - Godwin, Andrew K

AU - Kuderer, Nicole M

AU - Rader, Janet S

AU - Zuna, Rosemary E

AU - Sood, Anil K

AU - Lazar, Alexander J

AU - Ojesina, Akinyemi I

AU - Adebamowo, Clement

AU - Adebamowo, Sally N

AU - Baggerly, Keith A

AU - Chen, Ting-Wen

AU - Chiu, Hua-Sheng

AU - Lefever, Steve

AU - Liu, Liang

AU - MacKenzie, Karen

AU - Orsulic, Sandra

AU - Roszik, Jason

AU - Shelley, Carl Simon

AU - Song, Qianqian

AU - Vellano, Christopher P

AU - Wentzensen, Nicolas

AU - Weinstein, John N

AU - Mills, Gordon B

AU - Levine, Douglas A

AU - Akbani, Rehan

PY - 2018/4/9

Y1 - 2018/4/9

N2 - 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.

AB - 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.

KW - Breast Neoplasms/genetics

KW - DNA Copy Number Variations

KW - Databases, Genetic

KW - Female

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Gene Regulatory Networks

KW - Genetic Predisposition to Disease

KW - Genital Neoplasms, Female/genetics

KW - Humans

KW - Mutation

KW - Organ Specificity

KW - Prognosis

KW - RNA, Long Noncoding/genetics

KW - Receptors, Estrogen/genetics

UR - https://www.scopus.com/pages/publications/85044909989

U2 - 10.1016/j.ccell.2018.03.014

DO - 10.1016/j.ccell.2018.03.014

M3 - Article

C2 - 29622464

SN - 1535-6108

VL - 33

SP - 690-705.e9

JO - Cancer cell

JF - Cancer cell

IS - 4

ER -

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

Abstract

Keywords

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