Loss of parental-specific methylation at the IGF2 locus in human hepatocellular carcinoma.

Significant production of the growth factor IGF2 has been reported in human hepatocellular carcinomas (HCCs). Disturbances associated with changes in methylation at this locus or affecting the 11p15.5 imprinting domain as a whole can be postulated in HCCs. In the present study, the methylation status of differentially methylated regions of the imprinted genes TSSC5, LIT1, and IGF2, which span the 11p15 domain, was analysed in 71 liver tissues from virus-associated and non-virus-associated HCCs compared with six normal liver tissues. Altered methylation of TSSC5 and LIT1 was observed in only 6% and 8% of HCCs, respectively, compared with 89% at the IGF2 locus, suggesting that these loci were not concomitantly dysregulated. These observations suggest that loss of parental-specific methylation at the IGF2 locus may be specifically associated with HCC, whether virus-associated or non-virus-associated, and arising in cirrhotic or non-cirrhotic livers. Copyright 2003 John Wiley & Sons, Ltd.