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PLoS Genet. 2007 Sep;3(9):1709-23. Epub 2007 Jul 31.

Comparing the DNA hypermethylome with gene mutations in human colorectal cancer.

Author information

1
Cancer Biology Division, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA. kornels@jhmi.edu

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 tumor-specific 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.

PMID:
17892325
PMCID:
PMC1988850
DOI:
10.1371/journal.pgen.0030157
[Indexed for MEDLINE]
Free PMC Article

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