Journal article
Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer
Cell, Vol.173(2), pp.291-304.e6
04/05/2018
DOI: 10.1016/j.cell.2018.03.022
PMCID: PMC5957518
PMID: 29625048
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.
Details
- Title: Subtitle
- Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer
- Creators
- Katherine A Hoadley - University of North Carolina at Chapel HillChristina Yau - Buck Institute for Research on AgingToshinori Hinoue - Van Andel InstituteDenise M Wolf - University of California, San FranciscoAlexander J Lazar - The University of Texas MD Anderson Cancer CenterEsther Drill - Memorial Sloan Kettering Cancer CenterRonglai Shen - Memorial Sloan Kettering Cancer CenterAlison M Taylor - Harvard UniversityAndrew D Cherniack - Broad InstituteVésteinn Thorsson - Institute for Systems BiologyRehan Akbani - The University of Texas MD Anderson Cancer CenterReanne Bowlby - BC Cancer AgencyChristopher K Wong - University of California, Santa CruzMaciej Wiznerowicz - Poznan University of Medical SciencesFrancisco Sanchez-Vega - Memorial Sloan Kettering Cancer CenterA Gordon Robertson - BC Cancer AgencyBarbara G Schneider - Vanderbilt UniversityMichael S Lawrence - Harvard UniversityHoutan Noushmehr - Henry Ford Health SystemTathiane M Malta - Universidade de São PauloJoshua M Stuart - University of California, Santa CruzChristopher C Benz - Buck Institute for Research on AgingPeter W Laird - Van Andel Institute
- Contributors
- Cancer Genome Atlas Network (Contributor)Deqin Ma (Contributor) - University of Iowa, PathologyMohammed M Milhem (Contributor) - University of Iowa, Internal MedicineAaron D Bossler (Contributor) - University of Iowa, Pathology
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.173(2), pp.291-304.e6
- DOI
- 10.1016/j.cell.2018.03.022
- PMID
- 29625048
- PMCID
- PMC5957518
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Grant note
- U24 CA143843 / NCI NIH HHS U24 CA199461 / NCI NIH HHS P30 CA016086 / NCI NIH HHS U24 CA210957 / NCI NIH HHS U54 HG003079 / NHGRI NIH HHS P30 CA016672 / NCI NIH HHS P30 ES010126 / NIEHS NIH HHS U24 CA143883 / NCI NIH HHS U24 CA210990 / NCI NIH HHS U24 CA143799 / NCI NIH HHS U24 CA210988 / NCI NIH HHS R50 CA221675 / NCI NIH HHS U24 CA143867 / NCI NIH HHS U24 CA143858 / NCI NIH HHS U24 CA210974 / NCI NIH HHS U24 CA143882 / NCI NIH HHS P30 CA008748 / NCI NIH HHS U54 HG003067 / NHGRI NIH HHS U24 CA143845 / NCI NIH HHS U24 CA143835 / NCI NIH HHS U54 HG003273 / NHGRI NIH HHS U24 CA143840 / NCI NIH HHS U24 CA144025 / NCI NIH HHS U24 CA143866 / NCI NIH HHS U24 CA210950 / NCI NIH HHS U24 CA210949 / NCI NIH HHS U24 CA143848 / NCI NIH HHS R01 CA163722 / NCI NIH HHS
- Language
- English
- Date published
- 04/05/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
- Record Identifier
- 9984185172602771
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