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Quantitative, genome-wide analysis of the DNA methylome in sporadic pituitary adenomas.
MedLine Citation:
PMID:  23045325     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
DNA methylation is one of several epigenetic modifications that together with genetic aberrations are hallmarks of tumourigenesis including those emanating from the pituitary gland. In this study we examined DNA methylation across 27578 CpG sites spanning more than 14000 genes in the major pituitary adenoma subtypes. Genome-wide changes were first determined in a discovery cohort comprising, non-functioning (NF), growth hormone (GH), prolactin secreting (PRL) and corticotroph (CT) adenoma relative to post-mortem pituitaries. Using stringent cut-off criteria we validated increased methylation by pyrosequencing in 12 of 16 (75%) genes. Overall these criteria identified 40 genes in NF, 21 in GH, 6 in PRL and 2 in CT hat were differentially methylated relative to controls. In a larger independent cohort of adenomas, for genes where hypermethylation had been validated, different frequencies of hypermethylation were apparent; where the KIAA1822 and TFAP2E genes were hypermethylated in 12 of 13 NF adenomas whereas the COL1A2 gene showed increase in 2 of 13 adenomas. For genes showing differential methylation across and between adenoma subtypes pyrosequencing confirmed these findings. For 3 of 12 genes investigated, an inverse relationship between methylation and transcript expression was observed where increased methylation of, EML2, RHOD and HOXB1 is associated with significantly reduced transcript expression. This study provides the first, genome-wide survey of adenoma, subtype-specific epigenomic changes and will prove useful for identification of biomarkers that perhaps predict or characterise growth patterns. The functional characterisation of identified genes will also provide insight of tumour aetiology and identification of new therapeutic targets.
Authors:
Cuong V Duong; Richard D Emes; Frank Wessely; Kiren Yacqub-Usman; Richard N Clayton; William E Farrell
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  Endocrine-related cancer     Volume:  -     ISSN:  1479-6821     ISO Abbreviation:  Endocr. Relat. Cancer     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9436481     Medline TA:  Endocr Relat Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
C Duong, ISTM, Keele University, Stoke on Trent, United Kingdom.
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