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

The Cancer Genome Atlas Network

Research output: Contribution to journalArticle

136 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)291-304.e6
JournalCell
Volume173
Issue number2
DOIs
StatePublished - Apr 5 2018

Fingerprint

Tumors
Tissue
Histology
Methylation
Oncology
Chromosomes
MicroRNAs
Cluster Analysis
Neoplasms
Genes
Messenger RNA
DNA
Aneuploidy
Proteins
Protein Array Analysis
Atlases
DNA Methylation
Genome
Kidney
Direction compound

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer. / The Cancer Genome Atlas Network.

In: Cell, Vol. 173, No. 2, 05.04.2018, p. 291-304.e6.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Network. / Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer. In: Cell. 2018 ; Vol. 173, No. 2. pp. 291-304.e6.
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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.",
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