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

Hoadley, Katherine A; Yau, Christina; Hinoue, Toshinori; Wolf, Denise M; Lazar, Alexander J; Drill, Esther; Shen, Ronglai; Taylor, Alison M; Cherniack, Andrew D; Thorsson, Vésteinn; Akbani, Rehan; Bowlby, Reanne; Wong, Christopher K; Wiznerowicz, Maciej; Sanchez-Vega, Francisco; Robertson, A Gordon; Schneider, Barbara G; Lawrence, Michael S; Noushmehr, Houtan; Malta, Tathiane M; ... (2018). Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer. Cell, 173(2), 291-304.e6. Cell Press 10.1016/j.cell.2018.03.022

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0092-8674

Publisher:

Cell Press

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

09 Oct 2019 11:03

Last Modified:

22 Oct 2019 16:30

Publisher DOI:

10.1016/j.cell.2018.03.022

PubMed ID:

29625048

Additional Information:

Mark Rubin (Direktor DBMR) ist Collaborator in dieser Publikation.

Uncontrolled Keywords:

TCGA cancer cell-of-origin genome methylome organs proteome subtypes tissues transcriptome

BORIS DOI:

10.7892/boris.126378

URI:

https://boris.unibe.ch/id/eprint/126378

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