Loss of imprinting of IGF2 and H19 in osteosarcoma is accompanied by reciprocal methylation changes of a CTCF-binding site Journal Article
| Authors: | Ulaner, G. A.; Vu, T. H.; Li, T.; Hu, J. F.; Yao, X. M.; Yang, Y.; Gorlick, R.; Meyers, P.; Healey, J.; Ladanyi, M.; Hoffman, A. R. |
| Article Title: | Loss of imprinting of IGF2 and H19 in osteosarcoma is accompanied by reciprocal methylation changes of a CTCF-binding site |
| Abstract: | The adjacent insulin-like growth factor 2 (IGF2) and H19 genes are imprinted in most normal human tissues, but imprinting is often lost in tumors. The mechanisms involved in maintenance of imprinting (MOI) and loss of imprinting (LOI) are unresolved. We show here that osteosarcoma (OS) tumors with IGF2/H19 MOI exhibit allele-specific differential methylation of a CTCF-binding site upstream of H19. LOI of IGF2 or H19 in OS occurs in a mutually exclusive manner, and occurs with monoallelic expression of the other gene. Bisulfite sequencing reveals IGF2 LOI occurs with biallelic CpG methylation of the CTCF-binding site, while H19 LOI occurs with biallelic hypomethylation of this site. Our data demonstrate that IGF2 LOI and H19 LOI are accompanied by reciprocal methylation changes at a critical CTCF-binding site. We propose a model in which incomplete gain or loss of methylation at this CTCF-binding site during tumorigenesis explains the complex and often conflicting expression patterns of IGF2 and H19 in tumors. |
| Keywords: | osteosarcoma; controlled study; human tissue; human cell; major clinical study; promoter region; dna-binding proteins; genetic analysis; polymerase chain reaction; allele; gene expression; genotype; dna methylation; carcinogenesis; transcription factors; cpg island; nucleotide sequence; binding site; binding sites; rna, untranslated; tumor suppressor protein; zinc finger protein; repressor proteins; genome imprinting; genomic imprinting; protein methylation; somatomedin b; genetic polymorphism; bisulfite; experimental model; insulin-like growth factor ii; humans; human; priority journal; article |
| Journal Title: | Human Molecular Genetics |
| Volume: | 12 |
| Issue: | 5 |
| ISSN: | 0964-6906 |
| Publisher: | Oxford University Press |
| Date Published: | 2003-04-15 |
| Start Page: | 535 |
| End Page: | 549 |
| Language: | English |
| DOI: | 10.1093/hmg/ddg034 |
| PUBMED: | 12588801 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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