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Horm Metab Res 2005; 37(6): 361-368
DOI: 10.1055/s-2005-870153
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© Georg Thieme Verlag KG Stuttgart · New York

Epigenetic Mechanisms of Tumorigenesis

W.  E.  Farrell1
  • 1 Institute of Science and Technology in Medicine, School of Medicine, Keele University, Stoke on Trent, Staffordshire, UK
Research in the author’s laboratory is jointly supported by the Samantha Dickson Research Trust and the UK Brain Tumor Society.
Further Information

Publication History

Received 16 August 2004

Accepted after revision 30 September 2004

Publication Date:
07 July 2005 (online)

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Abstract

In the majority of human cancers, heritable loss of gene function through cell division may be mediated as often by epigenetic as by genetic abnormalities. Epigenetic modification occurs through a process of interrelated changes in CpG island methylation and histone modifications. Candidate gene approaches of cell cycle, growth regulatory and apoptotic genes have shown epigenetic modification associated with loss of cognate proteins in sporadic pituitary tumors. A search for novel genes on the basis of their differential methylation has led to the isolation and functional characterization of a pro-apoptotic mediator - a pituitary tumor apoptosis gene (PTAG). Although PTAG expression is significantly underexpressed in most pituitary adenomas, mechanisms in addition to methylation most likely account for its loss. The GNAS gene is imprinted in normal pituitary, and activating mutations within Gsα, referred to as the gsp oncogene, are almost invariably associated with the maternal expressed allele in somatotrophic adenomas. In addition, epigenetic modification, manifesting as relaxation of imprinting, leads to biallelic expression of Gsα irrespective of gsp status. Pituitary tumors as components of familial syndromes represent a rare entity, and the role of epigenetic modification in their evolution and outgrowth is not known. Although speculative, these studies might provide new insight since methylation-associated gene silencing is a feature of other familial tumor types.

Key words

Epigenetics - Pituitary tumors - Familial - TSG (Tumor-suppressor gene)

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Prof. W. E. Farrell

Institute of Science and Technology in Medicine, School of Medicine

Keele University · Stoke on Trent · Staffordshire · ST4 7QB · UK

Phone: + 44 (1782) 55 52 25

Fax: + 44 (1782) 74 73 19

Email: w.e.farrell@keele.ac.uk

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