| Evidence for the role of aberrant DNA methylation in the pathogenesis of Lynch syndrome adenomas. | |
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MedLine Citation:
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PMID: 17278092 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Colorectal cancer (CRC) forms through a series of histologic steps that are accompanied by mutations and epigenetic alterations, which is called the polyp-cancer sequence. The role of epigenetic alterations, such as aberrant DNA methylation, in the polyp-cancer sequence in sporadic CRC and particularly in hereditary colon cancer is not well understood. Consequently, we assessed the methylation status of CDKN2A/p16, MGMT, MLH1 and p14(ARF) in adenomas arising in the Lynch syndrome, a familial colon cancer syndrome caused by MLH1 and MSH2 mutations, to determine if DNA methylation is a "second hit" mechanism in CRC and to characterize the role of DNA methylation in the polyp phase of the Lynch syndrome. We found MLH1 and p14(ARF) are methylated in 53 and 60% of the Lynch syndrome adenomas and in 4 and 20% of sporadic adenomas, whereas CDKN2A/p16 and MGMT are methylated in 6 and 14% of the Lynch syndrome adenomas versus 50 and 64% of sporadic adenomas. Therefore, the frequency and pattern of gene methylation varies between the Lynch syndrome and sporadic colon adenomas, implying differences in the molecular pathogenesis of the tumors. MLH1 methylation in the Lynch syndrome adenomas suggests gene methylation might have a role in the initiation of these neoplasms. |
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Authors:
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Andrew Kaz; Young-Ho Kim; Slavomir Dzieciatkowski; Henry Lynch; Patrice Watson; Mary Kay Washington; Li Lin; William M Grady |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 120 ISSN: 0020-7136 ISO Abbreviation: Int. J. Cancer Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-03-08 Completed Date: 2007-04-17 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 1922-9 Citation Subset: IM |
Copyright Information:
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(c) 2007 Wiley-Liss, Inc. |
Affiliation:
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Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing Adenoma / genetics* Adult Aged Carrier Proteins / genetics Colonic Neoplasms / genetics* Colorectal Neoplasms, Hereditary Nonpolyposis / etiology, genetics* DNA Methylation* DNA Modification Methylases DNA Repair Enzymes Female Genes, p16 Humans Loss of Heterozygosity Male Middle Aged Nuclear Proteins / genetics Tumor Suppressor Protein p14ARF / genetics Tumor Suppressor Proteins |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Carrier Proteins; 0/MLH1 protein, human; 0/Nuclear Proteins; 0/Tumor Suppressor Protein p14ARF; 0/Tumor Suppressor Proteins; EC 2.1.1.-/DNA Modification Methylases; EC 2.1.1.63/MGMT protein, human; EC 6.5.1.-/DNA Repair Enzymes |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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