Overexpression of a fish CDKN2 gene in a hereditary melanoma model

The fish genus Xiphophorus provides a vertebrate model useful in etiologica l studies of cancer. Hybrid fish can spontaneously develop melanomas derivi ng from the inheritance of melanistic pigment patterns and the simultaneous absence of proper genetic regulation. A cyclin-dependent kinase inhibitor gene, termed CDKN2X; was mapped to a genomic region that is implicated in f ish melanoma tumor suppression, The related human tumor suppressor locus CD KN2A (P16, INK4A, II MTS1) is deleted, mutated or transcriptionally repress ed through methylation of cytosine bases within the 5' CpG island in a vari ety of neoplasms, including melanoma, The fish CDKN2X locus harbors a CPG i sland within its promoter and first exon, analogous in location to CpG isla nds in human CDKN2A and CDKN2B loci. The methylation state of individual Cp G dinucleotides was investigated in genomic DNA derived from control tissue s and melanomas within the CDKN2X 5' CpG island, The studied genomic area w as found to be virtually unmethylated in all tested tissues including melan omas, In addition, RNA expression studies of the fish CDKN2X locus revealed that it is significantly overexpressed in melanoma, in contrast to what ha s been reported for the human CDKN2A locus in melanoma, Such overexpression may be a consequence of the pronounced upregulation of the Xmrk-2 receptor tyrosine kinase oncogene reported in several Xiphophorus melanoma models.