Aberrant DNA methylation associated with MTHFR C677T genetic polymorphism in cutaneous squamous cell carcinoma in renal transplant patients.
Laing, M E Cummins, R O'Grady, A O'Kelly, P Kay, E W Murphy, G M
Laing, M E
Cummins, R
O'Grady, A
O'Kelly, P
Kay, E W
Murphy, G M
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Editors
Other Contributors
Date
2010-08
Date Submitted
Keywords
Other Subjects
Subject 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
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
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
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.
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.
Language
en
ISSN
1365-2133
eISSN
ISBN
DOI
10.1111/j.1365-2133.2010.09774.x
PMID
20346029