Aberrant DNA methylation associated with MTHFR C677T genetic polymorphism in cutaneous squamous cell carcinoma in renal transplant patients.

Hdl Handle:
http://hdl.handle.net/10147/127126
Title:
Aberrant DNA methylation associated with MTHFR C677T genetic polymorphism in cutaneous squamous cell carcinoma in renal transplant patients.
Authors:
Laing, M E; Cummins, R; O'Grady, A; O'Kelly, P; Kay, E W; Murphy, G M
Affiliation:
Department of Dermatology, RCSI ERC Smurfit Building, Beaumont Hospital, Dublin 9, Ireland. mrylaing@yahoo.co.uk
Citation:
Aberrant DNA methylation associated with MTHFR C677T genetic polymorphism in cutaneous squamous cell carcinoma in renal transplant patients. 2010, 163 (2):345-52 Br. J. Dermatol.
Journal:
The British journal of dermatology
Issue Date:
Aug-2010
URI:
http://hdl.handle.net/10147/127126
DOI:
10.1111/j.1365-2133.2010.09774.x
PubMed ID:
20346029
Abstract:
Changes in genomic DNA methylation associated with cancer include global DNA hypomethylation and gene-specific hyper- or hypomethylation. We have previously identified a genetic variant in the MTHFR gene involved in the methylation pathway which confers risk for the development of squamous cell carcinoma (SCC) in renal transplant patients. This genetic variant has also been discovered to confer SCC risk in nontransplant patients with low folate status.; To explore the methylation profile of SCC compared with adjacent non-neoplastic skin using pyrosequencing, and to elucidate whether the MTHFR polymorphism impacts upon the methylation patterns in SCC.; We used pyrosequencing to evaluate global (using long interspersed nuclear element 1) and gene-specific (p16 and MGMT) methylation status in 47 SCCs and 40 adjacent autologous non-neoplastic skin samples in those with (n = 16) and without (n = 17) the MTHFR polymorphism.; Pyrosequencing methylation analysis revealed that SCC was hypomethylated compared with adjacent non-neoplastic skin (P < 0.04). Patients with the MTHFR polymorphism had higher levels of global methylation in tumours and non-neoplastic skin compared with those without the MTHFR polymorphism (P < 0.002). There was no association between levels of methylation in tumour and non-neoplastic skin for the genes MGMT and p16.; Global hypomethylation appears to be a feature of SCC. Aberrant methylation of DNA appears related to polymorphisms of MTHFR. Such findings suggest that intervention in the form of demethylating agents or folate supplementation might be beneficial in the treatment or prevention of SCC.
Item Type:
Article
Language:
en
MeSH:
Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; DNA Methylation; Female; Humans; Kidney Transplantation; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Neoplasm Proteins; Polymorphism, Genetic; Sequence Analysis, DNA; Skin Neoplasms
ISSN:
1365-2133

Full metadata record

DC FieldValue Language
dc.contributor.authorLaing, M Een
dc.contributor.authorCummins, Ren
dc.contributor.authorO'Grady, Aen
dc.contributor.authorO'Kelly, Pen
dc.contributor.authorKay, E Wen
dc.contributor.authorMurphy, G Men
dc.date.accessioned2011-04-05T10:04:54Z-
dc.date.available2011-04-05T10:04:54Z-
dc.date.issued2010-08-
dc.identifier.citationAberrant DNA methylation associated with MTHFR C677T genetic polymorphism in cutaneous squamous cell carcinoma in renal transplant patients. 2010, 163 (2):345-52 Br. J. Dermatol.en
dc.identifier.issn1365-2133-
dc.identifier.pmid20346029-
dc.identifier.doi10.1111/j.1365-2133.2010.09774.x-
dc.identifier.urihttp://hdl.handle.net/10147/127126-
dc.description.abstractChanges in genomic DNA methylation associated with cancer include global DNA hypomethylation and gene-specific hyper- or hypomethylation. We have previously identified a genetic variant in the MTHFR gene involved in the methylation pathway which confers risk for the development of squamous cell carcinoma (SCC) in renal transplant patients. This genetic variant has also been discovered to confer SCC risk in nontransplant patients with low folate status.-
dc.description.abstractTo explore the methylation profile of SCC compared with adjacent non-neoplastic skin using pyrosequencing, and to elucidate whether the MTHFR polymorphism impacts upon the methylation patterns in SCC.-
dc.description.abstractWe used pyrosequencing to evaluate global (using long interspersed nuclear element 1) and gene-specific (p16 and MGMT) methylation status in 47 SCCs and 40 adjacent autologous non-neoplastic skin samples in those with (n = 16) and without (n = 17) the MTHFR polymorphism.-
dc.description.abstractPyrosequencing methylation analysis revealed that SCC was hypomethylated compared with adjacent non-neoplastic skin (P < 0.04). Patients with the MTHFR polymorphism had higher levels of global methylation in tumours and non-neoplastic skin compared with those without the MTHFR polymorphism (P < 0.002). There was no association between levels of methylation in tumour and non-neoplastic skin for the genes MGMT and p16.-
dc.description.abstractGlobal hypomethylation appears to be a feature of SCC. Aberrant methylation of DNA appears related to polymorphisms of MTHFR. Such findings suggest that intervention in the form of demethylating agents or folate supplementation might be beneficial in the treatment or prevention of SCC.-
dc.language.isoenen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshCarcinoma, Squamous Cell-
dc.subject.meshDNA Methylation-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshKidney Transplantation-
dc.subject.meshMale-
dc.subject.meshMethylenetetrahydrofolate Reductase (NADPH2)-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Proteins-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshSequence Analysis, DNA-
dc.subject.meshSkin Neoplasms-
dc.titleAberrant DNA methylation associated with MTHFR C677T genetic polymorphism in cutaneous squamous cell carcinoma in renal transplant patients.en
dc.typeArticleen
dc.contributor.departmentDepartment of Dermatology, RCSI ERC Smurfit Building, Beaumont Hospital, Dublin 9, Ireland. mrylaing@yahoo.co.uken
dc.identifier.journalThe British journal of dermatologyen
dc.description.provinceLeinster-

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