Three animal melanoma models have recently been identified in livebearing fishes of the genus Xiphophorus, comprising platyfish and swordtail species. Two of these are spontaneous melanomas occurring in different platyfish interspecies backcross hybrids; the other melanoma is LTV-induced in platyfish-swordtail backcross hybrids. It is likely that both spontaneous melanomas are regulated in tumor progression by tumor susceptibility genes that have not been previously characterized; the UV-induced melanoma has only been recently studied and its genetic regulation is as yet unknown. The genetic linkage map of Xiphophorus is the most complete of the few established in fishes, with 75 pigment, DNA, and protein markers distributed on as many as 20 of the 24 chromosome pairs. Therefore, by multipoint linkage analysis of allozyme and RFLP markers cosegregating with melanoma phenotype in backcross hybrids, genetic factors regulating progression to malignancy can readily be identified and characterized in these tumor models. Since there is evidence of genetic heterogeneity in human melanoma susceptibility, a synthesis of the results of investigating animal melanoma models with multiple genetic elements will promote a better understanding of the underlying genetic factors in melanoma formation and progression to malignancy in humans. To realize this overall goal, our specific aims are: (1) To analyze the genetic regulation of two recently described Xiphophorus interspecies spontaneous hybrid melanomas using multipoint linkage analysis to identify and map genetic regulatory elements, with the goal of identifying tumor susceptibility loci; (2) To investigate the genetic basis of a Xiphophorus hybrid melanoma useful as an animal model for UV-induced malignant progression by analyzing genetic factors that may contribute to LTV induction of melanomas; (3) To clone and sequence cDNAs that may be involved in tumorigenesis in Xiphophorus hybrid melanomas, including Xiphophorus erbB and RB homologues; and (4) To approach the molecular cloning of a known tumor suppressor gene by marker saturation using anonymous DNA RFLPs.
| Rahn, Jennifer J; Trono, David; Gimenez-Conti, Irma et al. (2009) Etiology of MNU-induced melanomas in Xiphophorus hybrids. Comp Biochem Physiol C Toxicol Pharmacol 149:129-33 |
| Butler, Andrew P; Trono, David; Coletta, Luis Della et al. (2007) Regulation of CDKN2A/B and Retinoblastoma genes in Xiphophorus melanoma. Comp Biochem Physiol C Toxicol Pharmacol 145:145-55 |
| Butler, Andrew P; Trono, David; Beard, Rebecca et al. (2007) Melanoma susceptibility and cell cycle genes in Xiphophorus hybrids. Mol Carcinog 46:685-91 |
| Kazianis, Steven; Khanolkar, Vandeeta A; Nairn, Rodney S et al. (2004) Structural organization, mapping, characterization and evolutionary relationships of CDKN2 gene family members in Xiphophorus fishes. Comp Biochem Physiol C Toxicol Pharmacol 138:291-9 |
| Rudd, Michael D; Johnston, Dennis A; Kazianis, Steven et al. (2003) Cloning and analysis of a FoxO transcription factor from Xiphophorus. Gene 302:31-41 |
| Kazianis, S; Gimenez-Conti, I; Setlow, R B et al. (2001) MNU induction of neoplasia in a platyfish model. Lab Invest 81:1191-8 |
| Kazianis, S; Coletta, L D; Morizot, D C et al. (2000) Overexpression of a fish CDKN2 gene in a hereditary melanoma model. Carcinogenesis 21:599-605 |
| Kazianis, S; Morizot, D C; Coletta, L D et al. (1999) Comparative structure and characterization of a CDKN2 gene in a Xiphophorus fish melanoma model. Oncogene 18:5088-99 |
| Morizot, D C; McEntire, B B; Della Coletta, L et al. (1998) Mapping of tyrosine kinase gene family members in a Xiphophorus melanoma model. Mol Carcinog 22:150-7 |
| McConnell, T J; Godwin, U B; Norton, S F et al. (1998) Identification and mapping of two divergent, unlinked major histocompatibility complex class II B genes in Xiphophorus fishes. Genetics 149:1921-34 |
Showing the most recent 10 out of 21 publications
