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      Genetic and environmental melanoma models in fish

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          Abstract

          Experimental animal models are extremely valuable for the study of human diseases, especially those with underlying genetic components. The exploitation of various animal models, from fruitflies to mice, has led to major advances in our understanding of the etiologies of many diseases, including cancer. Cutaneous malignant melanoma is a form of cancer for which both environmental insult (i.e., UV) and hereditary predisposition are major causative factors. Fish melanoma models have been used in studies of both spontaneous and induced melanoma formation. Genetic hybrids between platyfish and swordtails, different species of the genus Xiphophorus, have been studied since the 1920s to identify genetic determinants of pigmentation and melanoma formation. Recently, transgenesis has been used to develop zebrafish and medaka models for melanoma research. This review will provide a historical perspective on the use of fish models in melanoma research, and an updated summary of current and prospective studies using these unique experimental systems.

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          Patterns of somatic mutation in human cancer genomes.

          Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.
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            The Tol2kit: a multisite gateway-based construction kit for Tol2 transposon transgenesis constructs.

            Transgenesis is an important tool for assessing gene function. In zebrafish, transgenesis has suffered from three problems: the labor of building complex expression constructs using conventional subcloning; low transgenesis efficiency, leading to mosaicism in transient transgenics and infrequent germline incorporation; and difficulty in identifying germline integrations unless using a fluorescent marker transgene. The Tol2kit system uses site-specific recombination-based cloning (multisite Gateway technology) to allow quick, modular assembly of [promoter]-[coding sequence]-[3' tag] constructs in a Tol2 transposon backbone. It includes a destination vector with a cmlc2:EGFP (enhanced green fluorescent protein) transgenesis marker and a variety of widely useful entry clones, including hsp70 and beta-actin promoters; cytoplasmic, nuclear, and membrane-localized fluorescent proteins; and internal ribosome entry sequence-driven EGFP cassettes for bicistronic expression. The Tol2kit greatly facilitates zebrafish transgenesis, simplifies the sharing of clones, and enables large-scale projects testing the functions of libraries of regulatory or coding sequences. Copyright 2007 Wiley-Liss, Inc.
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              Melanoma.

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                Author and article information

                Journal
                Pigment Cell Melanoma Res
                pcr
                Pigment Cell & Melanoma Research
                Blackwell Publishing Ltd
                1755-1471
                1755-148X
                June 2010
                08 March 2010
                : 23
                : 3
                : 314-337
                Affiliations
                [1 ]simpleInstitute for Genetics and Molecular Medicine, MRC Human Genetics Unit and The Division of Cancer Research, The University of Edinburgh Edinburgh, UK
                [2 ]simpleDepartment of Carcinogenesis, Science Park-Research Division, The University of Texas M.D. Anderson Cancer Center Smithville, TX, USA
                [3 ]simpleGraduate School of Biomedical Sciences, The University of Texas Houston, TX, USA
                Author notes
                Rodney S. Nairn, e-mail: rnairn@ 123456mdanderson.org and E. Elizabeth Patton, e-mail: epatton@ 123456staffmail.ed.ac.uk

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                Article
                10.1111/j.1755-148X.2010.00693.x
                2881310
                20230482
                1eb593e1-1c57-41ab-a6d9-f09a4b2e4737
                © 2010 Blackwell Munksgaard

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 21 January 2010
                : 28 February 2010
                : 28 February 2010
                Categories
                Review Articles

                Dermatology
                zebrafish,medaka,melanoma,uv,xiphophorus
                Dermatology
                zebrafish, medaka, melanoma, uv, xiphophorus

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