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

Cell. Volume 173 Issue 2: p291–304.e6, 5 April 2018 10.1016/j.cell.2018.03.022

We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens representing 33 types of cancer. We performed molecular clustering on chromosome arm-level aneuploidy, DNA hypermethylation, mRNA and miRNA expression levels and reverse phase protein arrays individually, of which all, except for aneuploidy, revealed clustering organized primarily by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA methylation-based clustering, even after exclusion of 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, Pan-Squamous cancers, and those related by stemness features, which in turn may inform treatment strategies.

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