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

The Cancer Genome Atlas Research Network

doi:10.1016/j.cell.2014.06.049

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

The Cancer Genome Atlas Research Network

Department of Developmental Biology and Cancer Research

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

1046 Scopus citations

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-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.

Original language	American English
Pages (from-to)	929-944
Number of pages	16
Journal	Cell
Volume	158
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2014.06.049
State	Published - 14 Aug 2014

Bibliographical note

Funding Information:
We thank the thousands of patients and their loved ones who contributed materially, emotionally, and intellectually to this study. We thank D.A. Wheeler and M.L. Meyerson for scientific review of the work and M.P. Schroeder for help setting up Gitools. We thank K.R. Shaw, B.A. Ozenberger, H.J. Sofia, C.M. Hutter, and J.C. Zenklusen for administrative support. This work was supported by grants from the Chapman Foundation and Dell Foundation to J.N.W., a MD Anderson Physician Scientist Award to L.A.B., a Burroughs Welcome Career Award at the Scientific Interface to B.J.R., and support from the following grants from the United States National Institutes of Health: K08 CA137153, K08 CA176561, P50 CA083639, R01 CA071468, R01 HG005690, R01 HG007069, R01CA180006, R21 CA155679, U01 CA168394, U24 CA143858, U24 CA143867-05, U24 CA143883, U24 CA143848, U24 CA143858, U24 CA143866, U54 CA112970, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, U54 HG003273, U54 HG003067, U54 HG003079, ZIA-DC-000073, ZIA-DC-000074, and P30 CA016672 for the MD Anderson CCSG Functional Proteomics Core.

Publisher Copyright:
© 2014 Elsevier Inc.

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10.1016/j.cell.2014.06.049

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@article{348bfc9b9df64100ba430522d2814d3f,

title = "Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin",

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-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.",

author = "{The Cancer Genome Atlas Research Network} and Hoadley, {Katherine A.} and Christina Yau and Wolf, {Denise M.} and Cherniack, {Andrew D.} and David Tamborero and Sam Ng and Leiserson, {Max D.M.} and Beifang Niu and McLellan, {Michael D.} and Vladislav Uzunangelov and Jiashan Zhang and Cyriac Kandoth and Rehan Akbani and Hui Shen and Larsson Omberg and Andy Chu and Margolin, {Adam A.} and {Van't Veer}, {Laura J.} and Nuria Lopez-Bigas and Laird, {Peter W.} and Raphael, {Benjamin J.} and Li Ding and Robertson, {A. Gordon} and Byers, {Lauren A.} and Mills, {Gordon B.} and Weinstein, {John N.} and {Van Waes}, Carter and Zhong Chen and Collisson, {Eric A.} and Benz, {Christopher C.} and Perou, {Charles M.} and Stuart, {Joshua M.} and Rachel Abbott and Scott Abbott and Aksoy, {B. Arman} and Kenneth Aldape and Adrian Ally and Samirkumar Amin and Dimitris Anastassiou and Auman, {J. Todd} and Baggerly, {Keith A.} and Miruna Balasundaram and Saianand Balu and Baylin, {Stephen B.} and Benz, {Stephen C.} and Berman, {Benjamin P.} and Brady Bernard and Bhatt, {Ami S.} and Inanc Birol and Black, {Aaron D.}",

note = "Funding Information: We thank the thousands of patients and their loved ones who contributed materially, emotionally, and intellectually to this study. We thank D.A. Wheeler and M.L. Meyerson for scientific review of the work and M.P. Schroeder for help setting up Gitools. We thank K.R. Shaw, B.A. Ozenberger, H.J. Sofia, C.M. Hutter, and J.C. Zenklusen for administrative support. This work was supported by grants from the Chapman Foundation and Dell Foundation to J.N.W., a MD Anderson Physician Scientist Award to L.A.B., a Burroughs Welcome Career Award at the Scientific Interface to B.J.R., and support from the following grants from the United States National Institutes of Health: K08 CA137153, K08 CA176561, P50 CA083639, R01 CA071468, R01 HG005690, R01 HG007069, R01CA180006, R21 CA155679, U01 CA168394, U24 CA143858, U24 CA143867-05, U24 CA143883, U24 CA143848, U24 CA143858, U24 CA143866, U54 CA112970, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, U54 HG003273, U54 HG003067, U54 HG003079, ZIA-DC-000073, ZIA-DC-000074, and P30 CA016672 for the MD Anderson CCSG Functional Proteomics Core. Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",

year = "2014",

month = aug,

day = "14",

doi = "10.1016/j.cell.2014.06.049",

language = "American English",

volume = "158",

pages = "929--944",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

AU - The Cancer Genome Atlas Research Network

AU - Hoadley, Katherine A.

AU - Yau, Christina

AU - Wolf, Denise M.

AU - Cherniack, Andrew D.

AU - Tamborero, David

AU - Ng, Sam

AU - Leiserson, Max D.M.

AU - Niu, Beifang

AU - McLellan, Michael D.

AU - Uzunangelov, Vladislav

AU - Zhang, Jiashan

AU - Kandoth, Cyriac

AU - Akbani, Rehan

AU - Shen, Hui

AU - Omberg, Larsson

AU - Chu, Andy

AU - Margolin, Adam A.

AU - Van't Veer, Laura J.

AU - Lopez-Bigas, Nuria

AU - Laird, Peter W.

AU - Raphael, Benjamin J.

AU - Ding, Li

AU - Robertson, A. Gordon

AU - Byers, Lauren A.

AU - Mills, Gordon B.

AU - Weinstein, John N.

AU - Van Waes, Carter

AU - Chen, Zhong

AU - Collisson, Eric A.

AU - Benz, Christopher C.

AU - Perou, Charles M.

AU - Stuart, Joshua M.

AU - Abbott, Rachel

AU - Abbott, Scott

AU - Aksoy, B. Arman

AU - Aldape, Kenneth

AU - Ally, Adrian

AU - Amin, Samirkumar

AU - Anastassiou, Dimitris

AU - Auman, J. Todd

AU - Baggerly, Keith A.

AU - Balasundaram, Miruna

AU - Balu, Saianand

AU - Baylin, Stephen B.

AU - Benz, Stephen C.

AU - Berman, Benjamin P.

AU - Bernard, Brady

AU - Bhatt, Ami S.

AU - Birol, Inanc

AU - Black, Aaron D.

N1 - Funding Information: We thank the thousands of patients and their loved ones who contributed materially, emotionally, and intellectually to this study. We thank D.A. Wheeler and M.L. Meyerson for scientific review of the work and M.P. Schroeder for help setting up Gitools. We thank K.R. Shaw, B.A. Ozenberger, H.J. Sofia, C.M. Hutter, and J.C. Zenklusen for administrative support. This work was supported by grants from the Chapman Foundation and Dell Foundation to J.N.W., a MD Anderson Physician Scientist Award to L.A.B., a Burroughs Welcome Career Award at the Scientific Interface to B.J.R., and support from the following grants from the United States National Institutes of Health: K08 CA137153, K08 CA176561, P50 CA083639, R01 CA071468, R01 HG005690, R01 HG007069, R01CA180006, R21 CA155679, U01 CA168394, U24 CA143858, U24 CA143867-05, U24 CA143883, U24 CA143848, U24 CA143858, U24 CA143866, U54 CA112970, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, U54 HG003273, U54 HG003067, U54 HG003079, ZIA-DC-000073, ZIA-DC-000074, and P30 CA016672 for the MD Anderson CCSG Functional Proteomics Core. Publisher Copyright: © 2014 Elsevier Inc.

PY - 2014/8/14

Y1 - 2014/8/14

N2 - 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.

AB - 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.

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U2 - 10.1016/j.cell.2014.06.049

DO - 10.1016/j.cell.2014.06.049

M3 - Article

C2 - 25109877

AN - SCOPUS:84908460595

SN - 0092-8674

VL - 158

SP - 929

EP - 944

JO - Cell

JF - Cell

IS - 4

ER -

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

Abstract

Bibliographical note

UN SDGs

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