Exploration of drug-response mechanism by integrating genetics and epigenetics across cancers

Abstract

Aim: To discover CpG island methylator phenotype (CIMP) as a predictor for cancer drug-response mechanism. Materials & methods: CIMP classification of 966 cancer cell lines was determined according to identified copy number alteration and differential methylation by DNA methylation profiles. CIMP-related drugs were analyzed by analysis of variance. Tissue–cell–drug networks were developed to predict drug response of individual samples. Results & conclusion: One hundred and thirty-six copy number gain and 142 copy number loss cell lines were classified into CIMP-high and CIMP-low groups, meanwhile 9 and 24 CIMP-associated drugs were identified, respectively. Specially, breast invasive carcinoma samples primarily composed by HCC1419 were predicted to be sensitive to GSK690693. The study provides guidance for drug response in cancer therapy through genome-wide DNA methylation.