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Cell. 2014 Aug 14;158(4):929-44. doi: 10.1016/j.cell.2014.06.049. Epub 2014 Aug 7.

Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin.

Collaborators (307)

Abbott R, Abbott S, Aksoy BA, Aldape K, Ally A, Amin S, Anastassiou D, Auman JT, Baggerly KA, Balasundaram M, Balu S, Baylin SB, Benz SC, Berman BP, Bernard B, Bhatt AS, Birol I, Black AD, Bodenheimer T, Bootwalla MS, Bowen J, Bressler R, Bristow CA, Brooks AN, Broom B, Buda E, Burton R, Butterfield YS, Carlin D, Carter SL, Casasent TD, Chang K, Chanock S, Chin L, Cho DY, Cho J, Chuah E, Chun HJ, Cibulskis K, Cirello G, Cleland J, Cline M, Craft B, Creighton CJ, Danilova L, Davidsen T, Davis C, Dees ND, Delenhaunty K, Demchok JA, Dhalla N, DiCara D, Dinh H, Dobson JR, Dodda D, Doddapaneni H, Donehower L, Dooling DJ, Dresdner G, Drummond J, Eakin A, Edgerton M, Elred JM, Eley G, Ellrott K, Fan C, Fei S, Felau I, Frazer S, Freeman SS, Frick J, Fronick CC, Fullerton LL, Fulton R, Gabriel SB, Gao J, Gastier-Foster JM, Gehlenborg N, George M, Getz G, Gibbs R, Goldman M, Gonzalez-Perez A, Gross B, Guin R, Gunaratne P, Hadjipanayis A, Hamilton MP, Hamilton SR, Han L, Han Y, Harper HA, Haseley P, Haussler D, Hayes DN, Heiman DI, Helman E, Helsel C, Herbrich SM, Herman JG, Hinoue T, Hirst C, Hirst M, Holt RA, Hoyle AP, Iype L, Jacobsen A, Jeffreys SR, Jensen MA, Jones CD, Jones SJ, Ju Z, Jung J, Kahles A, Kahn A, Kalicki-Veizer J, Kalra D, Kanchi KL, Kane DW, Kim H, Kim J, Knijenburg T, Koboldt DC, Kovar C, Kramer R, Kreisberg R, Kucherlapati R, Ladanyi M, Lander ES, Larson DE, Lawrence MS, Lee D, Lee E, Lee S, Lee W, Lehmann KV, Leinonen K, Leraas KM, Lerner S, Levine DA, Lewis L, Ley TJ, Li HI, Li J, Li W, Liang H, Lichtenberg TM, Lin J, Lin L, Lin P, Liu W, Liu Y, Liu Y, Lorenzi PL, Lu C, Lu Y, Luquette LJ, Ma S, Magrini VJ, Mahadeshwar HS, Mardis ER, Margolin A, Marra MA, Mayo M, McAllister C, McGuire SE, McMichael JF, Melott J, Meng S, Meyerson M, Mieczkowski PA, Miller CA, Miller ML, Miller M, Moore RA, Morgan M, Morton D, Mose LE, Mungall AJ, Muzny D, Nguyen L, Noble MS, Noushmehr H, O'Laughlin M, Ojesina AI, Ou Yang TH, Ozenberger B, Pantazi A, Parfenov M, Park PJ, Parker JS, Paull E, Sekhar Pedamallu C, Pinhl T, Pohl C, Pot D, Protopopov A, Przytycka T, Radenbaugh A, Ramirez NC, Ramirez R, Rätsch G, Reid J, Ren XJ, Reva B, Reynolds SM, Rhie SK, Roach J, Rovira H, Ryan M, Saksena G, Salama S, Sander C, Santoso N, Schein JE, Schmidt H, Schultz N, Schumacher SE, Seidman J, Senbabaoglu Y, Seth S, Sharpe S, Shen R, Sheth M, Shi Y, Shmulevich I, Silva GO, Simons JV, Sinha R, Sipahimalani P, Smith SM, Sofia HJ, Sokolov A, Soloway MG, Song X, Sougnez C, Spellman P, Staudt L, Stewart C, Stojanov P, Su X, Sumer SO, Sun Y, Swatloski T, Tabak B, Tam A, Tan D, Tang J, Tarnuzzer R, Taylor BS, Thiessen N, Thorsson V, Triche T Jr, Van Den Berg DJ, Vandin F, Varhol RJ, Vaske CJ, Veluvolu U, Verhaak R, Voet D, Walker J, Wallis JW, Waltman P, Wan Y, Wang M, Wang W, Wang Z, Waring S, Weinhold N, Weisenberger DJ, Wendl MC, Wheeler D, Wilkerson MD, Wilson RK, Wise L, Wong A, Wu CJ, Wu CC, Wu HT, Wu J, Wylie T, Xi L, Xi R, Xia Z, Xu AW, Yang D, Yang L, Yang L, Yang Y, Yao J, Yao R, Ye K, Yoshihara K, Yuan Y, Yung AK, Zack T, Zeng D, Zenklusen JC, Zhang H, Zhang J, Zhang N, Zhang Q, Zhang W, Zheng S, Zhu J, Zmuda E, Zou L.

Abstract

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-of-origin 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 pan-cancer 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.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID:
25109877
[PubMed - indexed for MEDLINE]
PMCID:
PMC4152462
Free PMC Article

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