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Cause and consequences of genetic and epigenetic alterations in human cancer.

Sadikovic B, Al-Romaih K, Squire JA, Zielenska M - Curr. Genomics (2008)

Bottom Line: Moreover, genomic change ranges from single nucleotide mutations to gross chromosomal aneuploidy; which may or may not be associated with underlying genomic instability.In addition to changes in DNA and chromosomes, it has become evident that oncogenomic processes can be profoundly influenced by epigenetic mechanisms.In addition we consider the associated interactions of genetic and epigenetic processes in tumour onset and progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada;

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.

No MeSH data available.


Related in: MedlinePlus

Acquisition of genetic and epigenetic changes disrupts normal gene expression and provides selective advantage to cancer cells.
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Figure 1: Acquisition of genetic and epigenetic changes disrupts normal gene expression and provides selective advantage to cancer cells.

Mentions: It has become evident that there is a strong link between epigenetic disruptions of DNA methylation and regions of genomic instability in human cancer. While early studies focused primarily on DNA hypermethylation of tumour suppressors, an increasing body of evidence indicate that hypomethylation of oncogenes represents another epigenetic event common in tumourigenesis. In addition to directly affecting gene expression, DNA methylation plays an important role in maintenance of genomic stability, particularly by repressing repetitive genomic elements, disruption of which is closely related to genomic instability and chromosomal aberrations. Fig. (1) presents our model of tumour progression in which underlying genetic and epigenetic changes drive tumour evolution by disrupting both normal gene expression and gene dosage, while concurrently increasing genomic instability, and as a result providing selective advantage to newly formed tumour cells.


Cause and consequences of genetic and epigenetic alterations in human cancer.

Sadikovic B, Al-Romaih K, Squire JA, Zielenska M - Curr. Genomics (2008)

Acquisition of genetic and epigenetic changes disrupts normal gene expression and provides selective advantage to cancer cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2691666&req=5

Figure 1: Acquisition of genetic and epigenetic changes disrupts normal gene expression and provides selective advantage to cancer cells.
Mentions: It has become evident that there is a strong link between epigenetic disruptions of DNA methylation and regions of genomic instability in human cancer. While early studies focused primarily on DNA hypermethylation of tumour suppressors, an increasing body of evidence indicate that hypomethylation of oncogenes represents another epigenetic event common in tumourigenesis. In addition to directly affecting gene expression, DNA methylation plays an important role in maintenance of genomic stability, particularly by repressing repetitive genomic elements, disruption of which is closely related to genomic instability and chromosomal aberrations. Fig. (1) presents our model of tumour progression in which underlying genetic and epigenetic changes drive tumour evolution by disrupting both normal gene expression and gene dosage, while concurrently increasing genomic instability, and as a result providing selective advantage to newly formed tumour cells.

Bottom Line: Moreover, genomic change ranges from single nucleotide mutations to gross chromosomal aneuploidy; which may or may not be associated with underlying genomic instability.In addition to changes in DNA and chromosomes, it has become evident that oncogenomic processes can be profoundly influenced by epigenetic mechanisms.In addition we consider the associated interactions of genetic and epigenetic processes in tumour onset and progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada;

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.

No MeSH data available.


Related in: MedlinePlus