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A novel population health approach: using fish retinoblastoma gene profiles as a surrogate for humans

Rotchell, Jeanette M.; du Corbier, Frances A.; Stentiford, Grant D.; Lyons, Brett P.; Liddle, Andrew R.; Ostrander, Gary K.

Authors

Frances A. du Corbier

Grant D. Stentiford

Brett P. Lyons

Andrew R. Liddle

Gary K. Ostrander



Abstract

Retinoblastoma, a tumor suppressor gene, is frequently mutated in diverse types of human tumors. We have previously shown that two types of fish tumor, eye and liver, also possess mutant Rb genes. Our aim is to determine if the Rb allele status is linked to environmentally-induced cancer and whether this information in fish can be used to predict future phenotype. This is a proof-of-concept investigation to elucidate if fish may act as surrogates in assessing pollution-induced tumor incidence and inform regulatory authorities of potential long-term population health consequences. Marine flatfish, Limanda limanda, that display either normal liver histopathology. liver adenoma or liver hepatocellular carcinoma were analysed for the presence of Rb gene alterations. Several Rb alterations were detected in the fish displaying adenoma and carcinoma, and not in the surrounding normal tissue from the same individuals. The profile is similar to that reported in humans in that they spread across the gene, particularly exons 8-23, and a functionally important region of the protein. This Rb allele data was then used to build statistical classifier sets, linking Rb status with tumor pathology. Further flatfish caught from coastal-water areas of differing contaminant burden around the UK were subsequently analysed for the presence of Rb alterations. Using novel pattern matching statistics of the classifier sets compared with the coastal samples, the coastal fish were considered more similar to the characterised disease phenotype than the normal phenotype. Preliminary data suggests that using a statistical approach, based on classifying sets of histopathologically-defined tumor states, makes it possible to predict the phenotype of wild fish based on the status of the Rb allele. Since the Rb gene is orthologous, fish populations could act as surrogates for human populations in an eco-epidemiological investigation of the combined roles of genetics and environmental exposures in the tumorigenesis process. (C) 2008 Elsevier Inc. All rights reserved.

Journal Article Type Article
Publication Date 2009-03
Journal COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
Print ISSN 1532-0456
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 149
Issue 2
Pages 134-140
APA6 Citation Rotchell, J. M., du Corbier, F. A., Stentiford, G. D., Lyons, B. P., Liddle, A. R., & Ostrander, G. K. (2009). A novel population health approach: using fish retinoblastoma gene profiles as a surrogate for humans. Comparative Biochemistry and Physiology - Part C: Toxicology and Pharmacology, 149(2), (134-140). doi:10.1016/j.cbpc.2008.09.009. ISSN 1532-0456
DOI https://doi.org/10.1016/j.cbpc.2008.09.009
Keywords Rb gene; Tumor suppressor; Cancer; Fish; Retinoblastoma; Eco-epidemiology
Publisher URL https://www.sciencedirect.com/science/article/pii/S1532045608001701?via%3Dihub
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