Journal
PLOS GENETICS
Volume 3, Issue 9, Pages 1709-1723Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.0030157
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Funding
- NCI NIH HHS [P30 CA006973, R01 CA043318, CA06973-44, CA043318] Funding Source: Medline
- NIEHS NIH HHS [ES11858, R01 ES011858] Funding Source: Medline
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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.
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