LOSS OF HETEROZYGOSITY OF IMPRINTED GENES IN SV40 T T ANTIGEN-INDUCEDHEPATOCELLULAR CARCINOMAS/

Expression of the chromosomally linked Insulin-like Growth Factor II ( IGF-II) and H19 genes is regulated by parental imprinting during devel opment, since the maternally inherited IGF-II and the paternally inher ited H19 alleles are inactive in fetal tissues. Here we show that expr ession of IGF-II and H19 genes is activated in transgenic mice during SV40 Tag-induced hepatocarcinogenesis and that imprinting of both gene s is conserved in the liver tumors. Allelic imbalances of IGF-II and H 19 genes and other chromosome 7 markers were detected in one third (13 /39) of the hepatocellular carcinomas analysed. A strong bias on the a llele retained in the neoplasms was observed, since underrepresentatio n or complete loss of maternal chromosome 7 was recognised in 12/13 ca ses. High levels of IGF-II mRNA were expressed by all carcinomas with relative excess of paternal chromosome 7 alleles and suppressed H19 ex pression was found in the neoplasms lacking the maternal alleles. Over all the results indicate that expression of imprinted genes is involve d in progression of experimental liver tumors and suggest that the mur ine chromosome 7, whose loss may possibly cause the inactivation of a growth-inhibitory gene, is preferentially retained as paternal copy in the liver tumors because of parental imprinting of IGF-II gene.