Abstract
Both genetic and epigenetic changes contribute to development of human cancer. Oncogenomics has primarily focused on understanding the genetic basis of neoplasia, with less emphasis being placed on the role of epigenetics in tumourigenesis. Genomic alterations in cancer vary between the different types and stages, tissues and individuals. Moreover, genomic change ranges from single nucleotide mutations to gross chromosomal aneuploidy; which may or may not be associated with underlying genomic instability. Collectively, genomic alterations result in widespread deregulation of gene expression profiles and the disruption of signalling networks that control proliferation and cellular functions. In addition to changes in DNA and chromosomes, it has become evident that oncogenomic processes can be profoundly influenced by epigenetic mechanisms. DNA methylation is one of the key epigenetic factors involved in regulation of gene expression and genomic stability, and is biologically necessary for the maintenance of many cellular functions. While there has been considerable progress in understanding the impact of genetic and epigenetic mechanisms in tumourigenesis, there has been little consideration of the importance of the interplay between these two processes. In this review we summarize current understanding of the role of genetic and epigenetic alterations in human cancer. In addition we consider the associated interactions of genetic and epigenetic processes in tumour onset and progression. Furthermore, we provide a model of tumourigenesis that addresses the combined impact of both epigenetic and genetic alterations in cancer cells.
Highlights
It is well-established that an important part of the cancer etiology lies in stepwise accumulation of genetic changes [1]
The phenotypic outcomes of genetic changes in cancer have led to a general classification of cancer genes as either tumour suppressors, which are involved in inhibition of cell growth and survival, or oncogenes which promote these effects [2]
This review provides an overview of the literature including some recent developments that give insights into the important question of co-evolution of epigenetic changes in tumourigenesis and cancer progression
Summary
It is well-established that an important part of the cancer etiology lies in stepwise accumulation of genetic changes [1]. The major types of genetic changes that result in oncogene activation are mutations, chromosomal translocations, or gene amplifications.
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