We have isolated a dab (Limanda limanda) homologue of the human
retinoblastoma (Rb) tumor suppressor gene. The L. limanda partial Rb
cDNA encodes a partial predicted
protein of 753
amino acids. DNA sequence analysis with other vertebrate Rb sequences demonstrates that the L. limanda Rb
cDNA is highly conserved in regions of functional importance. The sequence reported herein, combined with the high degree of conservation observed in critical domains, has also facilitated an investigation of the molecular etiology of environmentally induced liver
tumor samples in a
feral fish species. Mutational alterations were detected in liver
adenoma samples, also in apparently "normal" regions of liver samples dissected from fish displaying
adenoma, but not in normal liver samples from otherwise healthy
feral fish. These results are the first reporting the appearance of Rb mutations in wild-caught fish and suggest that the molecular etiology of fish
cancer appears to involve Rb-implicated
tumorigenesis. The ecotoxicological relevance of the Rb mutations in
feral fish liver
tumors, in terms of future
genome instability and possible development of a genotoxicity
biomarker, is discussed.