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Genetics of liver cancer
Published in J. K. Cowell, Molecular Genetics of Cancer, 2003
A.-M. Hui, L. Sun, M. Makuuchi
Many lines of evidence have indicated that DNA hypermethylation plays several important roles in human hepatocarcinogenesis (Hui and Makuuchi, 1999). The HIC1 gene is a candidate tumor suppressor gene located at 17p13.3, near to the TP53 locus. Recently, we studied HIC1 mRNA expression, LOH and methylation status at the 17p13.3 (D17S5 locus) in HCC tissues, noncancerous liver tissues showing cirrhosis or chronic hepatitis and normal liver tissues (Kanai et al., 1999). DNA hypermethylation at D17S5 was detected (by a Southern blotting method using methylation-sensitive restriction enzymes) in 90% of the HCC tissues and 44% of the liver tissues showing chronic hepatitis or cirrhosis, but was not demonstrated in normal liver tissues. The HIC1 mRNA expression level was significantly lower in liver tissues with chronic hepatitis or cirrhosis than in normal liver tissues, and was decreased even more in HCC tissues. Given that both chronic hepatitis and cirrhosis can be precancerous conditions, these data suggest that DNA hypermethylation at the 17p13.3 locus and reduced HIC1 mRNA expression may be involved in the early stages of hepatocarcinogenesis. Moreover, the HIC1 mRNA expression levels were lower in poorly differentiated HCCs than in well or moderately differentiated ones, suggesting the possible involvement of HIC1 in tumor progression. LOH at the 17p13.3 locus was demonstrated in 54% of the HCCs in this series. DNA hypermethylation at 17p13.3 therefore seems to contribute to hepatocarcinogenesis by decreasing HIC1 expression and predisposing to allelic losses around this locus.
Genetic testing for high-grade osteosarcoma: a guide for future tailored treatments?
Published in Expert Review of Molecular Diagnostics, 2018
Claudia Maria Hattinger, Maria Pia Patrizio, Elisa Tavanti, Silvia Luppi, Federica Magagnoli, Piero Picci, Massimo Serra
Other studies demonstrated extensive increased methylation of the HIC ZBTB transcriptional repressor 1 (HIC1) gene promoter in HGOS clinical samples [63,64]. HIC1 is a candidate tumor suppressor gene that encodes a zinc finger transcriptional factor that represses transcription of class I histone deacetylases. In a first study, HIC1 promoter hypermethylation was reported in 2 out 12 pediatric HGOS, suggesting that it may play a role in at least a minority of HGOS [63].
Clinical and pre-clinical utility of genomics in medulloblastoma
Published in Expert Review of Neurotherapeutics, 2018
The transcriptional repressor Hypermethylated in cance 1 (hic1) is often epigenetically silenced in medulloblastoma. Together with Ptch1, Hic1 acts as a tumor suppressor silencing the transcription factor Atoh1 during granule cell precursor differentiation. The double heterozygous mice Ptch –/– Hic –/– allows for malignant transformation four times more frequently than Ptch mice alone [110].