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Cell DOI:10.1016/j.cell.2014.06.049

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

Publication TypeJournal Article
Year of Publication2014
AuthorsHoadley, 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, Veer, LJVan't, López-Bigas, N, Laird, PW, Raphael, BJ, Ding, L, A Robertson, G, Byers, LA, Mills, GB, Weinstein, JN, Van Waes, C, Chen, Z, Collisson, EA, Benz, CC, Perou, CM, Stuart, JM
Corporate AuthorsCancer Genome Atlas Research Network
JournalCell
Volume158
Issue4
Pages929-44
Date Published2014 Aug 14
ISSN1097-4172
KeywordsCluster Analysis, Humans, Neoplasms, Transcriptome
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0092-8674(14)00876-9
DOI10.1016/j.cell.2014.06.049
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25109877?dopt=Abstract

Alternate JournalCell
PubMed ID25109877
PubMed Central IDPMC4152462
Grant ListZIA DC000073 / DC / NIDCD NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
R01CA180006 / CA / NCI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
K08 CA137153 / CA / NCI NIH HHS / United States
P50 CA100632 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
K08 CA176561 / CA / NCI NIH HHS / United States
R21 CA176561 / CA / NCI NIH HHS / United States
R01 HG007069 / HG / NHGRI NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
U24 CA143867-05 / CA / NCI NIH HHS / United States
P50 CA098258 / CA / NCI NIH HHS / United States
U01 CA168394 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
R01 HG005690 / HG / NHGRI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U24 CA180951 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
R01 CA180006 / CA / NCI NIH HHS / United States
U54 CA112970 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
P01 CA101937 / CA / NCI NIH HHS / United States
R01 CA071468 / CA / NCI NIH HHS / United States
P50 CA083639 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
U24 CA14385 / CA / NCI NIH HHS / United States
R01 CA180778 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
P01 CA099031 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
ZIA DC000074 / DC / NIDCD NIH HHS / United States
R21 CA155679 / CA / NCI NIH HHS / United States