Fine mapping of smallest common regions of deletion on chromosome 12 in liver epithelial and hepatocellular carcinoma cell lines from B6C3F(1) and C3B6F(1) mice

Loss of chromosomes frequently accompanies the establishment of hepatic cell lines in mice. Previous cytogenetic and allelotype studies have revealed that loss of chromosomes 4 and 12 is particularly common. In the present study, fine-deletion mapping was performed for chromosome 12 using 44 liver epithelial (LE) and hepatocellular carcinoma (HCC) cell lines derived from a hybrid between C3H/HeJ (C3H) and C57BL/6J (B6) mice with a high density of polymorphic microsatellite markers. Examination using 15 markers demonstrated that, although 19 of 44 cell lines showed deletion of the whole or large segments of chromosome 12, 3 had very small-range loss. Analysis of the latter using additional markers detected the 2 smallest common regions of deletion (Scrd1 and -2) in the centromeric and telomeric portions. Scrd1 is syntenic to human chromosome 2p and Scrd2 to human chromosome 14q, a region frequently deleted in various types of tumor. Of the 22 cases with loss of heterozygosity, 19 showed loss of B6 alleles. Our results demonstrate that mouse chromosome 12 contains at least 2 independent suppressor loci and that loss of B6 genes may be more advantageous than C3H gene deletion for establishment of hepatic cell lines.