Document Detail


Sessile serrated adenomas and classical adenomas: an epigenetic perspective on premalignant neoplastic lesions of the gastrointestinal tract.
MedLine Citation:
PMID:  21154739     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The diagnosis of sessile serrated adenomas (SSAs) is challenging, and there is a great deal of interobserver variability amongst pathologists in differentiating SSAs from hyperplastic polyps (HPPs). The aim of this study was (i) to assess the utility of epigenetic changes such as DNA methylation in differentiating SSAs from HPPs and (ii) to identify common methylation based molecular markers potentially useful for early detection of premalignant neoplastic lesions of gastrointestinal tract. A total of 97 primary patient adenoma samples were obtained from The Johns Hopkins Hospital pathology archive with IRB approval and HIPAA compliance. We analyzed the promoter associated CpG island methylation status of 17 genes using nested multiplex methylation specific PCR (MSP). Methylation of CDX2, hMLH1 and TLR2 was detected in SSAs and SSAs with dysplasia but not in HPPs. A subset of genes including EVL, GATAs (4 and 5), HIN-1, SFRPs (1, 2, 4 and 5), SOX17 and SYNE1 were methylated frequently in all premalignant gastrointestinal adenomas including tubular adenomas, villous adenomas, SSAs and SSAs with dysplasia but infrequently in non-premalignant polyps such as HPPs. Methylation of CDX2, hMLH1 and TLR2 may be of diagnostic utility in differentiating, histologically challenging cases of SSAs from HPPs. Genes such as EVL, GATAs, HIN-1, SFRPs, SOX17 and SYNE1, which are frequently methylated in all types of tested premalignant adenomas, may be useful as biomarkers in stool-based strategies for early detection of these adenomas and CRCs in future.
Authors:
Mashaal Dhir; Shinichi Yachida; Leander Van Neste; Sabine C Glöckner; Jana Jeschke; Emmanouil P Pappou; Elizabeth A Montgomery; James G Herman; Stephen B Baylin; Christine Iacobuzio-Donahue; Nita Ahuja
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-11
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  129     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2012-06-27     Completed Date:  2012-09-13     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1889-98     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 UICC.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / genetics
Adenoma / diagnosis,  genetics*
Aged
Aged, 80 and over
Colonic Polyps / diagnosis,  genetics
CpG Islands
DNA Methylation*
Diagnosis, Differential
Female
Gastrointestinal Neoplasms / diagnosis*,  genetics*
Gene Expression Regulation, Neoplastic
Homeodomain Proteins / genetics
Humans
Hyperplasia
Male
Middle Aged
Nuclear Proteins / genetics
Precancerous Conditions / diagnosis*,  genetics*
Proto-Oncogene Proteins / genetics
Toll-Like Receptor 2 / genetics
ras Proteins / genetics
Grant Support
ID/Acronym/Agency:
K23 CA127141/CA/NCI NIH HHS; K23 CA127141-04/CA/NCI NIH HHS; K23CA127141/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/CDX2 protein, human; 0/Homeodomain Proteins; 0/KRAS protein, human; 0/MLH1 protein, human; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/TLR2 protein, human; 0/Toll-Like Receptor 2; EC 3.6.5.2/ras Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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