UMMS Affiliation

Department of Cell and Developmental Biology; Graduate School of Biomedical Sciences

Date

9-24-2013

Document Type

Article

Medical Subject Headings

Aged; Alleles; Carcinoma, Non-Small-Cell Lung; Cohort Studies; DNA Methylation; Female; Gene Expression; Genotype; Humans; Linkage Disequilibrium; Lung Neoplasms; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Multivariate Analysis; Polymorphism, Single Nucleotide; Testis

Disciplines

Cancer Biology | Medical Genetics | Molecular genetics | Neoplasms

Abstract

BACKGROUND: Tumor-specific, coordinate expression of cancer-testis (CT) genes, mapping to the X chromosome, is observed in more than 60% of non-small cell lung cancer (NSCLC) patients. Although CT gene expression has been unequivocally related to DNA demethylation of promoter regions, the underlying mechanism leading to loss of promoter methylation remains elusive. Polymorphisms of enzymes within the 1-carbon pathway have been shown to affect S-adenosyl methionine (SAM) production, which is the sole methyl donor in the cell. Allelic variants of several enzymes within this pathway have been associated with altered SAM levels either directly, or indirectly as reflected by altered levels of SAH and Homocysteine levels, and altered levels of DNA methylation. We, therefore, asked whether the five most commonly occurring polymorphisms in four of the enzymes in the 1-carbon pathway associated with CT gene expression status in patients with NSCLC.

METHODS: Fifty patients among a cohort of 763 with NSCLC were selected based on CT gene expression status and typed for five polymorphisms in four genes known to affect SAM generation by allele specific q-PCR and RFLP.

RESULTS: We identified a significant association between CT gene expression and the MTHFR 677 CC genotype, as well as the C allele of the SNP, in this cohort of patients. Multivariate analysis revealed that the genotype and allele strongly associate with CT gene expression, independent of potential confounders.

CONCLUSIONS: Although CT gene expression is associated with DNA demethylation, in NSCLC, our data suggests this is unlikely to be the result of decreased MTHFR function.

Rights and Permissions

Citation: Senses KM, Gonen M, Barutcu AR, Kalaylioglu Z, Isbilen M, Konu O, Chen YT, Altorki NK, Gure AO. Cancer-testis gene expression is associated with the methylenetetrahydrofolate reductase 677 C>T polymorphism in non-small cell lung carcinoma. BMC Med Genet. 2013 Sep 24;14:97. doi: 10.1186/1471-2350-14-97. Link to article on publisher's site

Comments

Copyright 2013 Senses et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Co-author Ahmet R. Barutcu is a doctoral student in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to Article in PubMed