Retinoblastoma gene mutations in chemically induced liver tumor samples of Japanese medaka (Oryzias latipes).

Abstract

Alterations in the retinoblastoma ( Rb) gene have been correlated with a large number and wide variety of human tumors, including hepatocellular carcinoma. We have previously characterized a medaka homologue of the human Rb complementary DNA that is conserved in regions of functional importance. Structural alterations in the entire coding region (exons 1 to 27) of the Rb gene in methylene-chloride-induced medaka liver tumors were investigated using polymerase chain reaction and single strand conformation polymorphism analysis. Four of 5 liver tumors were found to have Rb alterations. Sequencing revealed 7 point mutations in exons 18 and 23, resulting in 5 amino acid substitutions, and a deletion within exon 19. Our results suggest that the molecular etiology of the medaka hepatocellular carcinoma models appear similar to that reported in humans. As such, the medaka appears to be a valid model for the study of Rb-implicated tumorigenesis.