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Updated: Aug 13, 2026
Methylated DNA Immunoprecipitation
Published on: January 2, 2009
Epigenetic mechanisms of tumorigenesis
1Institute of Science and Technology in Medicine, School of Medicine, Keele University, Stoke on Trent, Staffordshire, UK. w.e.farrell@keele.ac.uk
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 Gsalpha, 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 Gsalpha 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.
Insights
Epigenetic abnormalities, like DNA methylation, significantly contribute to human cancers by silencing genes. This study identifies a new gene, PTAG, involved in apoptosis, and explores epigenetic changes in pituitary tumors.
Area of Science:
- Endocrinology
- Cancer Biology
- Epigenetics
Background:
- Epigenetic modifications, including DNA methylation and histone alterations, play a crucial role in gene function loss, comparable to genetic mutations in human cancers.
- Candidate gene studies in sporadic pituitary tumors reveal epigenetic alterations linked to the loss of cell cycle, growth regulatory, and apoptotic proteins.
Purpose of the Study:
- To investigate the role of epigenetic modifications in the development and progression of pituitary tumors.
- To identify novel genes affected by epigenetic changes in pituitary adenomas.
Main Methods:
- Differential methylation screening to identify novel genes.
- Functional characterization of identified genes, such as the pro-apoptotic mediator PTAG.
- Analysis of GNAS gene imprinting and its relaxation in pituitary tumors.
Main Results:
- PTAG, a novel pro-apoptotic gene, was isolated and functionally characterized; its underexpression in pituitary adenomas suggests a role in tumor development, though methylation may not be the sole cause of its loss.
- Relaxation of GNAS imprinting leads to biallelic GNAS expression in pituitary tumors, independent of gsp oncogene status.
- The role of epigenetic modifications in familial pituitary tumor syndromes remains largely unknown.
Conclusions:
- Epigenetic dysregulation, including altered DNA methylation and imprinting, is a significant factor in sporadic pituitary tumor pathogenesis.
- Further research into epigenetic mechanisms, particularly in familial syndromes, could offer new insights into tumor evolution and potential therapeutic strategies.
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