DNA methylation aberrancies delineate clinically distinct subsets of colorectal cancer and provide novel targets for epigenetic therapies

• Published in: Oncogene Vol. 37; no. 5; pp. 566 - 577
• Main Authors: Weisenberger, D J, Liang, G, Lenz, H-J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2018; Nature Publishing Group
• Subjects: 631/337/176/1988; 692/53/2421; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Biomarkers, Tumor - genetics; Carcinogenesis - genetics; Care and treatment; Cell Biology; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; CpG islands; CpG Islands - genetics; Deoxyribonucleic acid; Development and progression; DNA; DNA Demethylation - drug effects; DNA methylation; DNA Methylation - drug effects; DNA Methylation - genetics; DNA Modification Methylases - antagonists & inhibitors; DNA Modification Methylases - genetics; Epigenesis, Genetic - drug effects; Epigenesis, Genetic - genetics; Epigenetic inheritance; Epigenetics; Epigenomics - methods; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Gene Silencing; Genetic aspects; Health aspects; Human Genetics; Humans; Internal Medicine; Medicine; Medicine & Public Health; Metastases; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular Targeted Therapy - methods; Mutation; Oncogenes; Oncology; Prognosis; Proteomics; review; Risk factors; Tumorigenesis; Tumors
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2017.374

Colorectal cancer (CRC) is a worldwide health concern with respect to both incidence and mortality, and as a result, CRC tumorigenesis, progression and metastasis have been heavily studied, especially with respect to identifying genetic, epigenetic, transcriptomic and proteomic profiles of disease. DNA methylation alterations are hallmarks of CRC, and epigenetic driver genes have been identified that are thought to be involved in early stages of tumorigenesis. Moreover, distinct CRC patient subgroups are organized based on DNA methylation profiles. CRC tumors displaying CpG island methylator phenotypes (CIMPs), defined as DNA hypermethylation at specific CpG islands in subsets of tumors, show high concordance with specific genetic alterations, disease risk factors and patient outcome. This review details the DNA methylation alterations in CRC, the significance of CIMP status, the development of treatments based on specific molecular profiles and the application of epigenetic therapies for CRC patient treatment.