Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer Journal Article


Authors: Hoadley, K. A.; Yau, C.; Hinoue, T.; Wolf, D. M.; Lazar, A. J.; Drill, E.; Shen, R.; Taylor, A. M.; Cherniack, A. D.; Thorsson, V.; Akbani, R.; Bowlby, R.; Wong, C. K.; Wiznerowicz, M.; Sanchez-Vega, F.; Robertson, A. G.; Schneider, B. G.; Lawrence, M. S.; Noushmehr, H.; Malta, T. M.; The Cancer Genome Atlas Network; Stuart, J. M.; Benz, C. C.; Laird, P. W.
Article Title: Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer
Abstract: We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development. Comprehensive, integrated molecular analysis identifies molecular relationships across a large diverse set of human cancers, suggesting future directions for exploring clinical actionability in cancer treatment. © 2018 Elsevier Inc.
Keywords: adult; controlled study; human tissue; squamous cell carcinoma; proteome; chromosome; microrna; gene expression; dna methylation; histology; digestive system cancer; dna; messenger rna; microarray analysis; genome; kidney cancer; molecular biology; transcriptome; aneuploidy; tumor classification; cells; tissues; female genital tract cancer; methylome; subtypes; tcga; organs; cell-of-origin; cancer; human; male; female; priority journal; article; malignant neoplasm
Journal Title: Cell
Volume: 173
Issue: 2
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2018-04-05
Start Page: 291
End Page: 304.e6
Language: English
DOI: 10.1016/j.cell.2018.03.022
PROVIDER: scopus
PUBMED: 29625048
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
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MSK Authors
  1. Ronglai Shen
    127 Shen
  2. Esther Naomi Drill
    25 Drill