Dataset Information

Selection for a dominant oncogene and large male size as a risk factor for melanoma in the Xiphophorus animal model.

ABSTRACT: Adult height is a risk factor in numerous human cancers that involve aberrant receptor tyrosine kinase (RTK) signalling. However, its importance is debated due to conflicting epidemiological studies and the lack of useful in vivo models. In Xiphophorus fishes (Platyfishes/Swordtails), a functional RTK, Xiphophorus melanoma receptor kinase (Xmrk), serves as the dominant oncogene and has been maintained for several million years despite being deleterious and in an extremely unstable genomic region. Here we show that the Xmrk genotype is positively correlated with standard length in male and female wild caught Xiphophorus cortezi sampled throughout their phylogeographic distribution. Histopathology confirms the occurrence of malignant melanomas in both sexes; however, melanoma incidence was extremely male biased. Furthermore, males collected with malignant melanomas in the field were significantly larger than both Xmrk males collected without melanomas and wildtype (Xmrk deficient) males. These results not only provide a novel selective mechanism for the persistence of the germline Xmrk oncogene but also create an innovative avenue of melanoma research within the Xiphophorus fishes. Wildlife cancer in natural systems is a growing concern, therefore, future research investigating life history characteristics associated with certain phenotypes and genotypes that predispose an individual to cancer will be fundamental to increasing our understanding of the evolutionary biology of cancer in nature as well as in humans.

SUBMITTER: Fernandez AA

PROVIDER: S-EPMC2911510 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Selection for a dominant oncogene and large male size as a risk factor for melanoma in the Xiphophorus animal model.

Fernandez André A AA Bowser Paul R PR

Molecular ecology 20100801 15

Adult height is a risk factor in numerous human cancers that involve aberrant receptor tyrosine kinase (RTK) signalling. However, its importance is debated due to conflicting epidemiological studies and the lack of useful in vivo models. In Xiphophorus fishes (Platyfishes/Swordtails), a functional RTK, Xiphophorus melanoma receptor kinase (Xmrk), serves as the dominant oncogene and has been maintained for several million years despite being deleterious and in an extremely unstable genomic region ...[more]

PMID: 20618898

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Project description:Xiphophorus models are important for melanoma, sex determination and differentiation, ovoviviparity and evolution. To gain a global view of the molecular mechanism(s) whereby gene expression may influence sexual dimorphism in Xiphophorus and to develop a database for future studies, we performed a large-scale transcriptome study.The 454-FLX massively parallel DNA sequencing platform was employed to obtain 742,771 and 721,543 reads from 2 normalized cDNA libraries generated from whole adult female and male X. maculatus Jp 163 A, respectively. The reads assembled into 45,538 contigs (here, a "contig" is a set of contiguous sequences), of which, 11,918 shared homology to existing protein sequences. These numbers estimate that the contigs may cover 53% of the total number of Xiphophorus transcriptome. Putative translations were obtained for 11,918 cDNA contigs, of which, 3,049 amino acid sequences contain Pfam domains and 11,064 contigs encode secretory proteins. A total of 3,898 contigs were associated with 2,781 InterPro (IPR) entries and 5,411 contigs with 132 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. There were 10,446 contigs annotated with 69,778 gene ontology (GO) terms and the three corresponding organizing principles. Fifty-four potential sex differentially expressed genes have been identified from these contigs. Eight and nine of these contigs were confirmed by real-time PCR as female and male predominantly expressed genes respectively. Based on annotation results, 34 contigs were predicted to be differentially expressed in male and female and 17 of them were also confirmed by real-time PCR.This is the first report of an annotated overview of the transcriptome of X. maculatus and identification of sex differentially expressed genes. These data will be of interest to researchers using the Xiphophorus model. This work also provides an archive for future studies in molecular mechanisms of sexual dimorphism and evolution, and can be used in comparative studies of other fish.

Dataset Information

Selection for a dominant oncogene and large male size as a risk factor for melanoma in the Xiphophorus animal model.

Publications

Selection for a dominant oncogene and large male size as a risk factor for melanoma in the Xiphophorus animal model.

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