Isolation of the Retinoblastoma cDNA from the Marine Flatfish Dab (Limanda limanda) and Evidence of Mutational Alterations in Liver Tumors

du Corbier, Frances A, Stentiford, Grant D, Lyons, Brett P and Rotchell, Jeanette M (2005) Isolation of the Retinoblastoma cDNA from the Marine Flatfish Dab (Limanda limanda) and Evidence of Mutational Alterations in Liver Tumors. Environmental Science and Technology, 39 (24). pp. 9785-9790. ISSN 0013-936X

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Abstract

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.

Item Type: Article
Additional Information: There is concern that selected fish are prone to tumour formation. We report, for the first time, mutations implicated in tumour development. This was in collaboration with the UK regulatory authority, CEFAS. Corbier was a NERC-funded student supervised by me. I developed the concepts and wrote the paper.
Schools and Departments: School of Life Sciences > Biology and Environmental Science
Depositing User: Jeanette Rotchell
Date Deposited: 06 Feb 2012 20:50
Last Modified: 14 Jun 2012 11:14
URI: http://sro.sussex.ac.uk/id/eprint/28382
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