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Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma.

Honda S, Arai Y, Haruta M, Sasaki F, Ohira M, Yamaoka H, Horie H, Nakagawara A, Hiyama E, Todo S, Kaneko Y - Br. J. Cancer (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Diagnosis, Saitama Cancer Center, Research Institute for Clinical Oncology, 818 Komuro, Ina, Saitama 362-0806, Japan.

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.

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Representative data of RT–PCR analysis of PLAG1 mRNA. Numbers below lanes indicate the tumour number.
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fig5: Representative data of RT–PCR analysis of PLAG1 mRNA. Numbers below lanes indicate the tumour number.

Mentions: PLAG1 positively regulates IGF2, and its expression was detected in 12 tumours, foetal liver RNA and 2 cell lines, but not in 8 tumour and 3 normal liver tissues (Table 1 and Figure 5). The 12 tumours with PLAG1 mRNA expression showed higher levels of P4-specific IGF2 transcripts (P=0.01) and tended to show higher levels of P3-specific IGF2 transcripts (P=0.051) than the 8 tumours without PLAG1 expression. There was no significant difference in P2- or P1-specific transcript levels between tumours with and without PLAG1 mRNA expression.


Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma.

Honda S, Arai Y, Haruta M, Sasaki F, Ohira M, Yamaoka H, Horie H, Nakagawara A, Hiyama E, Todo S, Kaneko Y - Br. J. Cancer (2008)

Representative data of RT–PCR analysis of PLAG1 mRNA. Numbers below lanes indicate the tumour number.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600691&req=5

fig5: Representative data of RT–PCR analysis of PLAG1 mRNA. Numbers below lanes indicate the tumour number.
Mentions: PLAG1 positively regulates IGF2, and its expression was detected in 12 tumours, foetal liver RNA and 2 cell lines, but not in 8 tumour and 3 normal liver tissues (Table 1 and Figure 5). The 12 tumours with PLAG1 mRNA expression showed higher levels of P4-specific IGF2 transcripts (P=0.01) and tended to show higher levels of P3-specific IGF2 transcripts (P=0.051) than the 8 tumours without PLAG1 expression. There was no significant difference in P2- or P1-specific transcript levels between tumours with and without PLAG1 mRNA expression.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Diagnosis, Saitama Cancer Center, Research Institute for Clinical Oncology, 818 Komuro, Ina, Saitama 362-0806, Japan.

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.

Show MeSH
Related in: MedlinePlus