Comparing the DNA Hypermethylome with Gene Mutations in Human Colorectal Cancer

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.

Cited by papers we hold 9

• Research Progress of Epigenetics in Pathogenesis and Treatment of Malignant Tumors · 2020
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• Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood · 2019
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• Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment · 2018
  Corrected
• Promoter Hypermethylation of Tumour Suppressor Genes as Potential Biomarkers in Colorectal Cancer · 2015
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• Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers · 2014
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• LGR6 Is a High Affinity Receptor of R-Spondins and Potentially Functions as a Tumor Suppressor · 2012
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• Tissue of origin determines cancer-associated CpG island promoter hypermethylation patterns · 2012
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• Azacytidine and Decitabine Induce Gene-Specific and Non-Random DNA Demethylation in Human Cancer Cell Lines · 2011
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• Distinct High-Profile Methylated Genes in Colorectal Cancer · 2009
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