DNA methylation & tumor progression

Global DNA Methylation in the Modeling of Tumoral Progression

Yu-Wei Leu ¹ & Tim H.-M. Huang ²

¹ Human Epigenomics Ctr, Dept. of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan, 621
² Human Cancer Genetics Program, Dept. of Molecular Virology, Immunology, & Medical Genetics,
Comprehensive Cancer Ctr, The Ohio State University, Columbus, OH 43210, USA

Clonal selection and expansion in somatic cells determine the onset of tumors. Molecular events that are sufficient to trace the initiation and development of the somatic differences in tumors will become candidates for clinical biomarkers. Therefore, the process for identifying and characterizing tumoral biomarkers should examine the candidate molecular events for qualification, and this is the primary goal of this review. Global shifts in DNA methylation patterns are sufficient to change genome-wide gene expression and thereby cellular function. DNA methylation has also been proved to be one of the most dominant gene silencing mechanisms. These two observations link the DNA methylation of a gene and its function. Genetic data has revealed that the maintenance of normal DNA methylation status is crucial in preventing the onset of tumor formation, indicating the importance of regulating DNA methylation. Since DNA methylation can be initiated and transmitted in a lineage specific manner, any dominant silencing machinery, such as DNA methylation, represents an evolutionary chronicle of both normal and tumoral cell development. In fact, the existence of, and changes in DNA methylation patterns have come to represent the best indictor of switches in cellular status. More importantly, the initiation of DNA methylation is found to be influenced by certain environmental factors, such as viral infection or changes in food intake, and such events may trigger the initiation of methylation, possibly leading to cancer. Chronologically, the presence of DNA methylation foci within tumors links the spreading of DNA methylation to the onset of clonal expansion. The initiation of cancer is by nature polygenic, and can be easily uncovered by examining changes in methylation patterns in both space and time, providing us with the impetus to decode cancer epigenetics on a genomic scale. Some recent epigenomic studies of cancer will be discussed, focusing upon the most important findings.

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