Polymorphisms and methylation of the reduced folate carrier in osteosarcoma

Rui Yang, Jing Qin, Bang H. Hoang, John H. Healey, Richard Gorlick

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2046-2051
Number of pages6
JournalClinical Orthopaedics and Related Research
Volume466
Issue number9
DOIs
StatePublished - Sep 2008

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Reduced Folate Carrier Protein
Osteosarcoma
Methylation
3' Untranslated Regions
Methotrexate
DNA Methylation
Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Surgery

Cite this

Polymorphisms and methylation of the reduced folate carrier in osteosarcoma. / Yang, Rui; Qin, Jing; Hoang, Bang H.; Healey, John H.; Gorlick, Richard.

In: Clinical Orthopaedics and Related Research, Vol. 466, No. 9, 09.2008, p. 2046-2051.

Research output: Contribution to journalArticle

Yang, Rui ; Qin, Jing ; Hoang, Bang H. ; Healey, John H. ; Gorlick, Richard. / Polymorphisms and methylation of the reduced folate carrier in osteosarcoma. In: Clinical Orthopaedics and Related Research. 2008 ; Vol. 466, No. 9. pp. 2046-2051.
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