Polymorphisms and methylation of the reduced folate carrier in osteosarcoma Academic Article uri icon

Overview

MeSH Major

  • Bone Neoplasms
  • DNA Methylation
  • Folic Acid
  • Membrane Transport Proteins
  • Osteosarcoma
  • Polymorphism, Single-Stranded Conformational

abstract

  • High-dose methotrexate is a standard component in the treatment of osteogenic sarcoma. Impaired methotrexate uptake associated with decreased reduced folate carrier expression is a common mechanism of methotrexate resistance in osteogenic sarcoma samples. We investigated whether promoter methylation and polymorphisms in the 3' untranslated region are involved in regulating reduced folate carrier expression. In a cohort of 66 osteogenic sarcoma specimens, quantitative methylation-specific polymerase chain reaction and single-strand conformation polymorphism were performed. We found detectable levels of promoter methylation in 84.3% of samples. When related to the reduced folate carrier mRNA levels, a trend was observed that reduced folate carrier expression is lower in samples (median, 0.7) with greater than 10% DNA methylation as compared with those (median, 2.3) with less than 10% DNA methylation. The heterozygous polymorphisms of 2582 T/G and 2617C/T in the 3' untranslated region showed reduced folate carrier expression (median, 0.9) as compared with the wild-type 2582T and 2617C (median, 4.2). The data suggest promoter methylation and polymorphisms in the 3' untranslated region of the reduced folate carrier may be involved in its transcriptional regulation in osteogenic sarcoma. Further study is required to confirm this finding.

publication date

  • September 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2493020

Digital Object Identifier (DOI)

  • 10.1007/s11999-008-0323-3

PubMed ID

  • 18528741

Additional Document Info

start page

  • 2046

end page

  • 51

volume

  • 466

number

  • 9