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- Title
Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma.
- Authors
Honda, S.; Arai, Y.; Haruta, M.; Sasaki, F.; Ohira, M.; Yamaoka, H.; Horie, H.; Nakagawara, A.; Hiyama, E.; Todo, S.; Kaneko, Y.
- Abstract
IGF2, a maternally imprinted foetal growth factor gene, is implicated in many childhood tumours including hepatoblastoma (HB); however, the genetic and epigenetic alterations have not comprehensively been studied. We analysed the methylation status of the H19 differentially methylated region (DMR), loss of heterozygosity (LOH) and allelic expression of IGF2 in 54 HB tumours, and found that 12 tumours (22%) with LOH, 9 (17%) with loss of imprinting (LOI) and 33 (61%) with retention of imprinting (ROI). Biallelic and monoallelic IGF2 expressions correlated with hypermethylation and normal methylation of H19 DMR, respectively, in two tumours with LOI and seven tumours with ROI. Quantitative RT-PCR analysis showed minimal expression of H19 mRNA and substantial expression of IGF2 mRNA in tumours with LOH or LOI, and substantial expression of both H19 and IGF2 mRNAs in tumours with ROI. Increased IGF2 expression with predominant embryonic P3 transcript was found in the majority of HBs with ROI and foetal livers. In contrast to the earlier reports, our findings suggest that the disruption of the enhancer competition model reported in Wilms' tumour may also occur in HB. Both frequencies of LOH and LOI seem to be lower in HB than in Wilms' tumour, reflecting the different tissue origins.
- Subjects
TUMORS in children; GENOMIC imprinting; EPIGENESIS; METHYLATION; QUANTITATIVE research; RNA analysis; SOMATOMEDIN; REVERSE transcriptase polymerase chain reaction; RESEARCH; LIVER tumors; CANCER cells; GENETIC mutation; RESEARCH methodology; CYTOSKELETAL proteins; MEDICAL cooperation; EVALUATION research; DNA methylation; COMPARATIVE studies; GENES; DNA-binding proteins; POLYMERASE chain reaction
- Publication
British Journal of Cancer, 2008, Vol 99, Issue 11, p1891
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/sj.bjc.6604754