The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature.

<h4>Background</h4>Pituitary adenomas (PAs) are commonly occurring neoplasms with diverse endocrine and neurological effects. Although somatic gene mutations are uncommon in sporadic PAs, recent studies lend support to epigenetic modification as a potential cause of tumorigenesis and tum...

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Main Authors: Matthew Pease, Chao Ling, William J Mack, Kai Wang, Gabriel Zada
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0082619
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author Matthew Pease
Chao Ling
William J Mack
Kai Wang
Gabriel Zada
author_facet Matthew Pease
Chao Ling
William J Mack
Kai Wang
Gabriel Zada
author_sort Matthew Pease
collection DOAJ
description <h4>Background</h4>Pituitary adenomas (PAs) are commonly occurring neoplasms with diverse endocrine and neurological effects. Although somatic gene mutations are uncommon in sporadic PAs, recent studies lend support to epigenetic modification as a potential cause of tumorigenesis and tumor progression.<h4>Methods</h4>A systematic literature review of the PubMed and Google Scholar databases was conducted to identify abstracts (n=1,082) pertaining to key targets and mechanisms implicated in epigenetic dysregulation of PAs published between 1993-2013. Data regarding histopathological subtype, target genes, mode of epigenetic modification, and clinical correlation were recorded and analyzed.<h4>Results</h4>Of the 47 that studies met inclusion criteria and focused on epigenomic assessment of PAs, only 2 were genome-scale analyses. Current evidence supports epigenetic alteration in at least 24 PA genes, which were categorized into four groups based on function and epigenetic alteration: 1) Sixteen tumor suppressor genes silenced via DNA methylation; 2) Two oncogenes overexpressed via histone acetylation and hypomethylation; 3) Three imprinted genes with selective allelic silencing; and 4) One epigenome writer inducing abnormal genome-scale activity and 5) Two transcription regulators indirectly modifying the genome. Of these, 5 genes (CDKN2A, GADD45y, FGFR2, caspase-8, and PTAG) showed particular susceptibility to epigenetic modification, with abnormal DNA methylation in >50% of PA samples. Several genes displayed correlations between epigenetic modification and clinically relevant parameters, including invasiveness (CDKN2A; DAPK; Rb1), sex (MAGE-A3), tumor size (GNAS1), and histopathological subtype (CDKN2A; MEG3; p27; RASSF1A; Rb1).<h4>Conclusions</h4>Epigenetic modification of selected PA genes may play a key role in tumorigenesis and progression, which may translate into important diagnostic and therapeutic applications.
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spelling doaj-art-25d8960af4bd458dad23e1bef8b631ed2025-08-20T03:49:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8261910.1371/journal.pone.0082619The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature.Matthew PeaseChao LingWilliam J MackKai WangGabriel Zada<h4>Background</h4>Pituitary adenomas (PAs) are commonly occurring neoplasms with diverse endocrine and neurological effects. Although somatic gene mutations are uncommon in sporadic PAs, recent studies lend support to epigenetic modification as a potential cause of tumorigenesis and tumor progression.<h4>Methods</h4>A systematic literature review of the PubMed and Google Scholar databases was conducted to identify abstracts (n=1,082) pertaining to key targets and mechanisms implicated in epigenetic dysregulation of PAs published between 1993-2013. Data regarding histopathological subtype, target genes, mode of epigenetic modification, and clinical correlation were recorded and analyzed.<h4>Results</h4>Of the 47 that studies met inclusion criteria and focused on epigenomic assessment of PAs, only 2 were genome-scale analyses. Current evidence supports epigenetic alteration in at least 24 PA genes, which were categorized into four groups based on function and epigenetic alteration: 1) Sixteen tumor suppressor genes silenced via DNA methylation; 2) Two oncogenes overexpressed via histone acetylation and hypomethylation; 3) Three imprinted genes with selective allelic silencing; and 4) One epigenome writer inducing abnormal genome-scale activity and 5) Two transcription regulators indirectly modifying the genome. Of these, 5 genes (CDKN2A, GADD45y, FGFR2, caspase-8, and PTAG) showed particular susceptibility to epigenetic modification, with abnormal DNA methylation in >50% of PA samples. Several genes displayed correlations between epigenetic modification and clinically relevant parameters, including invasiveness (CDKN2A; DAPK; Rb1), sex (MAGE-A3), tumor size (GNAS1), and histopathological subtype (CDKN2A; MEG3; p27; RASSF1A; Rb1).<h4>Conclusions</h4>Epigenetic modification of selected PA genes may play a key role in tumorigenesis and progression, which may translate into important diagnostic and therapeutic applications.https://doi.org/10.1371/journal.pone.0082619
spellingShingle Matthew Pease
Chao Ling
William J Mack
Kai Wang
Gabriel Zada
The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature.
PLoS ONE
title The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature.
title_full The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature.
title_fullStr The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature.
title_full_unstemmed The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature.
title_short The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature.
title_sort role of epigenetic modification in tumorigenesis and progression of pituitary adenomas a systematic review of the literature
url https://doi.org/10.1371/journal.pone.0082619
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