DNA methylation and hepatocellular carcinoma.
The epigenetic makeup of organisms forms a link between the genetic information (DNA sequence) and the gene expression (and therefore phenotype). It dictates the memory for the gene expression pattern that, in turn, specifies cell identity. DNA methylation is the most studied epigenetic mechanism, aberration of which prevails in cancer, resulting in an altered pattern of gene expression and, therefore, cancerous features, including genetic abnormalities: mutations and genome instability. Altered methylation in cancer occurs in two directions. A marked reduction in the overall level of DNA methylation has been linked to the activation of transcription/transposition and the overexpression of protooncogenes. In parallel, there is a common occurrence of a hypermethylated status of the promoter cytosine (CpG) island in genes involved in the negative control of cell growth and in the maintenance of genomic stability; therefore causing transcription silencing. It is thus necessary and important to establish a comprehensive profile of DNA methylation changes in the promoter CpG island in many genes, both for better understanding of the underlying mechanisms and for diagnostic purposes in cancer clinics. Hepatocellular carcinoma is one of the most threatening malignancies in East Asia and Africa. In this short review, I briefly outline our current understanding of DNA methylation in cancer in general, emphasizing its recent progress in hepatocellular carcinoma.
Zhu
Jingde
J
Cancer Epigenetics and Gene Therapy Group, The State-Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, LN 2200/25, Xietu Road, Shanghai, 200032, China.
D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*
D014408:Biomarkers, Tumor