Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer.

Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ, Drill E, Shen R, Taylor AM, Cherniack AD, Thorsson V, Akbani R, Bowlby R, Wong CK, Wiznerowicz M, Sanchez-Vega F, Robertson AG, Schneider BG, Lawrence MS, Noushmehr H, Malta TM, Stuart JM, Benz CC, Laird PW (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Cell Elsevier

Book Volume: 173

Pages Range: 291-304.e6

Journal Issue: 2

DOI: 10.1016/j.cell.2018.03.022

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.

Involved external institutions

University of North Carolina at Chapel Hill US United States (USA) (US) Buck Institute for Research on Aging US United States (USA) (US) Van Andel Institute US United States (USA) (US) University of California San Francisco (UCSF) US United States (USA) (US) University of Texas MD Anderson Cancer Center US United States (USA) (US) Memorial Sloan Kettering Cancer Center US United States (USA) (US) Eli and Edythe L. Broad Institute of MIT and Harvard US United States (USA) (US) Institute for Systems Biology US United States (USA) (US) British Columbia Cancer Agency CA Canada (CA) Dana–Farber Cancer Institute US United States (USA) (US) Vanderbilt University US United States (USA) (US) Henry Ford Health System (HFHS) US United States (USA) (US) University of California Santa Cruz US United States (USA) (US)

How to cite

APA:

Hoadley, K.A., Yau, C., Hinoue, T., Wolf, D.M., Lazar, A.J., Drill, E.,... Laird, P.W. (2018). Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer. Cell, 173(2), 291-304.e6. https://doi.org/10.1016/j.cell.2018.03.022

MLA:

Hoadley, Katherine A., et al. "Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer." Cell 173.2 (2018): 291-304.e6.

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