Molecular mechanisms of genomic imprinting and clinical implications for cancer

Santiago Uribe-Lewis; Kathryn Woodfine; Lovorka Stojic; Adele Murrell

doi:10.1017/S1462399410001717

Molecular mechanisms of genomic imprinting and clinical implications for cancer

Published online by Cambridge University Press: 25 January 2011

Santiago Uribe-Lewis ,

Kathryn Woodfine ,

Lovorka Stojic and

Adele Murrell

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Santiago Uribe-Lewis: Affiliation:
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
Kathryn Woodfine: Affiliation:
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
Lovorka Stojic: Affiliation:
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
Adele Murrell*: Affiliation:
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
*: *Corresponding author: Adele Murrell, Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK. E-mail: adele.murrell@cancer.org.uk

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Abstract

Genomic imprinting is an epigenetic marking of genes in the parental germline that ensures the stable transmission of monoallelic gene expression patterns in a parent-of-origin-specific manner. Epigenetic marking systems are thus able to regulate gene activity independently of the underlying DNA sequence. Several imprinted gene products regulate cell proliferation and fetal growth; loss of their imprinted state, which effectively alters their dosage, might promote or suppress tumourigenic processes. Conversely, global epigenetic changes that underlie tumourigenesis might affect imprinted gene expression. Here, we review imprinted genes with regard to their roles in epigenetic predisposition to cancer, and discuss acquired epigenetic changes (DNA methylation, histone modifications and chromatin conformation) either as a result of cancer or as an early event in neoplasia. We also address recent work showing the potential role of noncoding RNA in modifying chromatin and affecting imprinted gene expression, and summarise the effects of loss of imprinting in cancer with regard to the roles that imprinted genes play in regulating growth signalling cascades. Finally, we speculate on the clinical applications of epigenetic drugs in cancer.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 13 , March 2011 , e2

DOI: https://doi.org/10.1017/S1462399410001717 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2011

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Molecular mechanisms of genomic imprinting and clinical implications for cancer

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Molecular mechanisms of genomic imprinting and clinical implications for cancer

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