Epigenetics vs. Gene Mutations in Colorectal Cancer

Stephen B. Baylin, M.D.
The Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University
NIEHS Grant R01ES011858

A large research team at John's Hopkins University led by NIEHS grantee Stephen Baylin has developed a new method they term a "transcriptome-wide approach" to identify genes susceptible to hypermethylation and transcriptional silencing in human colorectal cancer.

Using microarray technology, the new approach enables the identification of genes silenced by promoter hypermethylation and identifies candidate cancer genes in single tumors with a high degree of accuracy. The team estimates that nearly 5% of all known genes may be methylated in individual tumors. They found more hypermethylated genes than mutated genes in tumor tissue.

The study data indicate that for any cancer, failing to screen for both genetic and epigenetic changes may result in underestimating the full range of gene alterations and subsequent cellular pathway abnormalities. The overall findings point towards the need for genome-wide cancer gene screening efforts to include studying hypermethylated genes. These genes should be prioritized for sequencing to find mutations as well as prioritizing newly discovered mutations to be analyzed for methylation.

Citation: Schuebel KE, Chen W, Cope L, Glockner SC, Suzuki H, Yi JM, Chan TA, Van Neste L, Van Criekinge W, van den Bosch S, van Engeland M, Ting AH, Jair K, Yu W, Toyota M, Imai K, Ahuja N, Herman JG, Baylin SB. 2007. Comparing the DNA hypermethylome with gene mutations in human colorectal cancer. PLoS Genet 21;3(9):1709-1723. [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17892325&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)