Cell
Volume 158, Issue 4, 14 August 2014, Pages 929-944
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Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

https://doi.org/10.1016/j.cell.2014.06.049Get rights and content
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Highlights

  • New integrated cross-tumor-type classification carries prognostic information

  • Convergence of a multitissue squamous type

  • Divergence of bladder cancers into multiple pan-cancer subtypes

  • Rich resource for data-mining and biological discovery

Summary

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.

Cited by (0)

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Co-first author

21

Present address: Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97239-3098, USA

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Present address: Van Andel Research Institute, 333 Bostwick Avenue, Northeast, Grand Rapids, Michigan 49503, USA