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.

Graphical abstract

Keywords::

• ANOVA
• cancer
• classification
• copy number alteration
• CpG island methylator phenotype
• drug response
• network
• partial least squares
• quadratic programing
• TCGA

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2017-0162

Acknowledgements

The authors thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Financial & competing interests disclosure

This work is supported by the National Natural Science Foundation of China (grant numbers 81573021). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

The authors declare that they have no conflict of interests.

Additional information

Funding

This work is supported by the National Natural Science Foundation of China (grant numbers 81573021). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. The authors declare that they have no conflict of interests.