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

Katherine A Hoadley, Christina Yau, Denise M Wolf, Andrew D Cherniack, David Tamborero, Sam Ng, Max D M Leiserson, Beifang Niu, Michael D McLellan, Vladislav Uzunangelov, Jiashan Zhang, Cyriac Kandoth, Rehan Akbani, Hui Shen, Larsson Omberg, Andy Chu, Adam A Margolin, Laura J Van't Veer, Nuria Lopez-Bigas, Peter W Laird & 13 others Benjamin J Raphael, Li Ding, A Gordon Robertson, Lauren A Byers, Gordon B Mills, John N Weinstein, Carter Van Waes, Zhong Chen, Eric A Collisson, Christopher C Benz, Charles M Perou, Joshua M Stuart, Cancer Genome Atlas Research Network

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalCell
Volume158
Issue number4
Pages (from-to)929-44
Number of pages16
ISSN0092-8674
DOIs
Publication statusPublished - 14. Aug 2014

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Tissue
Neoplasms
Genes
Data Mining
Amplification
Data mining
Tumors
Lung
Proteomics
Datasets

Cite this

Hoadley, K. A., Yau, C., Wolf, D. M., Cherniack, A. D., Tamborero, D., Ng, S., ... Cancer Genome Atlas Research Network (2014). Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell, 158(4), 929-44. https://doi.org/10.1016/j.cell.2014.06.049
Hoadley, Katherine A ; Yau, Christina ; Wolf, Denise M ; Cherniack, Andrew D ; Tamborero, David ; Ng, Sam ; Leiserson, Max D M ; Niu, Beifang ; McLellan, Michael D ; Uzunangelov, Vladislav ; Zhang, Jiashan ; Kandoth, Cyriac ; Akbani, Rehan ; Shen, Hui ; Omberg, Larsson ; Chu, Andy ; Margolin, Adam A ; Van't Veer, Laura J ; Lopez-Bigas, Nuria ; Laird, Peter W ; Raphael, Benjamin J ; Ding, Li ; Robertson, A Gordon ; Byers, Lauren A ; Mills, Gordon B ; Weinstein, John N ; Van Waes, Carter ; Chen, Zhong ; Collisson, Eric A ; Benz, Christopher C ; Perou, Charles M ; Stuart, Joshua M ; Cancer Genome Atlas Research Network. / Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. In: Cell. 2014 ; Vol. 158, No. 4. pp. 929-44.
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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-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.",
author = "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 {Cancer Genome Atlas Research Network} and Fabio Vandin",
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Hoadley, KA, Yau, C, Wolf, DM, Cherniack, AD, Tamborero, D, Ng, S, Leiserson, MDM, Niu, B, McLellan, MD, Uzunangelov, V, Zhang, J, Kandoth, C, Akbani, R, Shen, H, Omberg, L, Chu, A, Margolin, AA, Van't Veer, LJ, Lopez-Bigas, N, Laird, PW, Raphael, BJ, Ding, L, Robertson, AG, Byers, LA, Mills, GB, Weinstein, JN, Van Waes, C, Chen, Z, Collisson, EA, Benz, CC, Perou, CM, Stuart, JM & Cancer Genome Atlas Research Network 2014, 'Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin', Cell, vol. 158, no. 4, pp. 929-44. https://doi.org/10.1016/j.cell.2014.06.049

Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. / Hoadley, Katherine A; Yau, Christina; Wolf, Denise M; Cherniack, Andrew D; Tamborero, David; Ng, Sam; Leiserson, Max D M; Niu, Beifang; McLellan, Michael D; Uzunangelov, Vladislav; Zhang, Jiashan; Kandoth, Cyriac; Akbani, Rehan; Shen, Hui; Omberg, Larsson; Chu, Andy; Margolin, Adam A; Van't Veer, Laura J; Lopez-Bigas, Nuria; Laird, Peter W; Raphael, Benjamin J; Ding, Li; Robertson, A Gordon; Byers, Lauren A; Mills, Gordon B; Weinstein, John N; Van Waes, Carter; Chen, Zhong; Collisson, Eric A; Benz, Christopher C; Perou, Charles M; Stuart, Joshua M; Cancer Genome Atlas Research Network.

In: Cell, Vol. 158, No. 4, 14.08.2014, p. 929-44.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

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

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 - Cancer Genome Atlas Research Network

AU - Vandin, Fabio

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

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-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.

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-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.

U2 - 10.1016/j.cell.2014.06.049

DO - 10.1016/j.cell.2014.06.049

M3 - Journal article

VL - 158

SP - 929

EP - 944

JO - Cell

JF - Cell

SN - 0092-8674

IS - 4

ER -