Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

被引：1088

作者：

Hoadley, Katherine A. ^{[1
]}

Yau, Christina ^{[2
]}

Wolf, Denise M. ^{[3
]}

Cherniack, Andrew D. ^{[4
]}

Tamborero, David ^{[5
]}

Ng, Sam ^{[6
]}

Leiserson, Max D. M. ^{[7
,8
]}

Niu, Beifang ^{[9
]}

McLellan, Michael D. ^{[9
]}

Uzunangelov, Vladislav ^{[6
]}

Zhang, Jiashan ^{[10
]}

Kandoth, Cyriac ^{[9
]}

Akbani, Rehan ^{[11
]}

Shen, Hui ^{[12
]}

Omberg, Larsson ^{[13
]}

Chu, Andy ^{[14
]}

Margolin, Adam A. ^{[13
]}

van't Veer, Laura J. ^{[3
]}

Lopez-Bigas, Nuria ^{[5
,15
]}

Laird, Peter W. ^{[12
]}

Raphael, Benjamin J. ^{[7
,8
]}

Ding, Li ^{[9
]}

Robertson, A. Gordon ^{[14
]}

Byers, Lauren A. ^{[11
]}

Mills, Gordon B. ^{[11
]}

Weinstein, John N. ^{[11
]}

Van Waes, Carter ^{[19
]}

Chen, Zhong ^{[20
]}

Collisson, Eric A. ^{[16
]}

Benz, Christopher C. ^{[2
]}

Perou, Charles M. ^{[1
,17
,18
]}

Stuart, Joshua M. ^{[6
]}

Abbott, Rachel

Abbott, Scott

Aksoy, B. Arman

Aldape, Kenneth

Ally, Adrian

Amin, Samirkumar

Anastassiou, Dimitris

Auman, J. Todd

Baggerly, Keith A.

Balasundaram, Miruna

Balu, Saianand

Baylin, Stephen B.

Benz, Stephen C.

Berman, Benjamin P.

Bernard, Brady

Bhatt, Ami S.

Birol, Inanc

Black, Aaron D.

机构：

[1] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[2] Buck Inst Res Aging, Novato, CA 94945 USA

[3] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94115 USA

[4] Harvard & MIT, Eli & Edythe Broad Inst, Cambridge, MA 02142 USA

[5] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Res Unit Biomed Informat, Barcelona 08003, Spain

[6] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Dept Biomol Engn, Santa Cruz, CA 95064 USA

[7] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA

[8] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA

[9] Washington Univ, Genome Inst, St Louis, MO 63108 USA

[10] NCI, NIH, Bethesda, MD 20892 USA

[11] UT MD Anderson Canc Ctr, Houston, TX 77030 USA

[12] Univ So Calif, Keck Sch Med, Epigenome Ctr, Los Angeles, CA 90033 USA

[13] Sage Bionetworks, Seattle, WA 98109 USA

[14] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada

[15] Catalan Inst Res & Adv Studies ICREA, Barcelona 08010, Spain

[16] Univ Calif San Francisco, Dept Med, San Francisco, CA 94148 USA

[17] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[18] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA

[19] NIDCD, NIH, Bethesda, MD 20892 USA

[20] NIDCD, NIH, Head & Neck Surg Branch, Bethesda, MD 20892 USA

来源：

CELL | 2014年 / 158卷 / 04期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

CELL LUNG-CANCER; MUTATIONS; CISPLATIN; MIGRATION; MODELS; GENES; HEAD;

D O I：

10.1016/j.cell.2014.06.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue'' disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-oforigin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pancancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.

引用

页码：929 / 944

页数：16

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