Polymorphisms and methylation of the reduced folate carrier in osteosarcoma Journal Article
| Authors: | Yang, R.; Qin, J.; Hoang, B. H.; Healey, J. H.; Gorlick, R. |
| Article Title: | Polymorphisms and methylation of the reduced folate carrier in osteosarcoma |
| 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. © 2008 The Association of Bone and Joint Surgeons. |
| Keywords: | osteosarcoma; adolescent; adult; child; clinical article; controlled study; human tissue; preschool child; aged; bone neoplasms; child, preschool; middle aged; bone tumor; carrier protein; methylation; promoter region; genetics; conference paper; comparative study; molecular genetics; polymerase chain reaction; metabolism; gene expression; genetic transcription; transcription, genetic; dna methylation; physiology; transcription regulation; messenger rna; rna, messenger; quantitative analysis; nucleotide sequence; down regulation; folic acid; 3' untranslated region; genetic polymorphism; membrane transport proteins; reduced folate carrier; single strand conformation polymorphism; polymorphism, single-stranded conformational; promoter regions (genetics) |
| Journal Title: | Clinical Orthopaedics and Related Research |
| Volume: | 466 |
| Issue: | 9 |
| ISSN: | 0009-921X |
| Publisher: | Springer |
| Date Published: | 2008-09-01 |
| Start Page: | 2046 |
| End Page: | 2051 |
| Language: | English |
| DOI: | 10.1007/s11999-008-0323-3 |
| PUBMED: | 18528741 |
| PROVIDER: | scopus |
| PMCID: | PMC2493020 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 17 November 2011" - "CODEN: CORTB" - "Molecular Sequence Numbers: GENBANK: U17920;" - "Source: Scopus" |
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