Comparing the DNA hypermethylome with gene mutations in human colorectal cancer

Kornel E. Schuebel, Wei Chen, Leslie Cope, Sabine C. Glöckner, Hiromu Suzuki, Joo Mi Yi, Timothy A. Chan, Leander Van Neste, Wim Van Criekinge, Sandra Van Den Bosch, Manon Van Engeland, Angela H. Ting, Kamwing Jair, Wayne Yu, Minoru Toyota, Kohzoh Imai, Nita Ahuja, James G. Herman, Stephen B. Baylin

Research output: Contribution to journalArticle

Abstract

We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island DNA hypermethylation and transcriptional silencing in colorectal cancer. By screening cell lines and validating tumorspecific hypermethylation in a panel of primary human colorectal cancer samples, we estimate that nearly 5% or more of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find larger numbers of genes hypermethylated in individual tumors, and a higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and to facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken.

Original languageEnglish (US)
Pages (from-to)1709-1723
Number of pages15
JournalPLoS genetics
Volume3
Issue number9
DOIs
StatePublished - Sep 2007

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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  • Cite this

    Schuebel, K. E., Chen, W., Cope, L., Glöckner, S. C., Suzuki, H., Yi, J. M., Chan, T. A., Van Neste, L., Van Criekinge, W., Van Den Bosch, S., Van Engeland, M., Ting, A. H., Jair, K., Yu, W., Toyota, M., Imai, K., Ahuja, N., Herman, J. G., & Baylin, S. B. (2007). Comparing the DNA hypermethylome with gene mutations in human colorectal cancer. PLoS genetics, 3(9), 1709-1723. https://doi.org/10.1371/journal.pgen.0030157