Development of the World's First In Vitro Cancer Epigenome Diagnostic through Biomarker Research for Personalized Cancer Treatment of RAS-wild-type Colorectal Cancer -Secondary Publication - Secondary Publication

Abstract

Epigenetic regulation mechanisms such as deoxy ribonucleic acid (DNA) methylation are important for controlling various biological phenomena by regulating gene expression at the genome level. Epigenetic abnormalities are associated with the onset of diseases including cancers. Aberrant DNA methylation is an important epigenetic change in the development and progression of colorectal cancer. DNA methylation in tumor tissues occurs mainly in CpG islands in the promoter regions of genes and inactivates gene functions by negatively suppressing transcription. The CpG island methylator phenotype (CIMP) is an important carcinogenic mechanism in colorectal cancer related to DNA methylation and is involved in approximately 20% of all colorectal cancers. However, CIMP does not always represent the genome-wide DNA methylation status in colorectal cancer. We developed a new method to assess genome-wide DNA methylation status and showed that it is a predictor of the efficacy of anti-estimated glomerular filtration rate (EGFR) antibody drugs and a prognostic factor. This new method has received regulatory approval as a new in vitro diagnostic for predicting sensitivity to anti-EGFR antibody drugs in colorectal cancer.