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Role of epigenome in tumorigenesis and drug resistance.

The last few decades have witnessed a tremendous advancement in understanding the genetic basis of major human diseases such as cancer. Intriguingly, there is also an evergrowing body of evidence that suggest the critical role of epigenetic regulation in pathogenesis. In contrast to genetic mechanisms often associated with changes in DNA sequence, epigenetics generally refers to the regulation of gene expression featuring alterations in histone modification, DNA methylation, chromatin conformation and non-coding RNAs, with the first two categories being the best-characterized so far. A growing list of epigenetic factors, including writers, readers and erasers have been identified, and huge differences in genome-wide epigenetic modifications, so-called epigenome, have been reported between normal tissues and cancer. Significantly, since the epigenetic regulation is largely dependent on enzymes, they are generally reversible and thus more amenable to pharmaceutical intervention. Hence, it is believed that a comprehensive understanding of how alterations in epigenome lead to tumorigenesis, progression and drug resistance is of primary importance to develop epigenetic therapies and to ensure long-term efficacy of cancer treatment.

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