MAPPING OF TYROSINE KINASE GENE FAMILY MEMBERS IN A XIPHOPHORUS MELANOMA MODEL

Xiphophorus fish have been the subject of intensive genetic research f or more than 60 yr, primarily because of the availability of a number of interspecific hybrids that are malignant melanoma models with appar ently simple oncogene and tumor suppressor gene determinants. The gene map of Xiphophorus is one of the most extensive among nonhuman verteb rates, with about 100 genes assigned to at least 20 independently asse rting linkage groups (LGs), as well as more than 250 anonymous DNA seq uence markers, providing coverage for most of the genome for genetic m apping studies. This characteristic has resulted in the mapping of a t umor suppressor locus, DIFF; which is one of two genetic determinants of melanoma formation in the best-studied hybrid melanoma, the Gordon- Kosswig melanoma model. The other gene responsible for melanoma format ion in this model is a sex-linked tyrosine kinase gene related to EGFR and called Xiphophorus melanoma receptor kinase (Xmrk). The cellular oncogene homologues of the non-receptor tyrosine kinase family ortholo gous to yes and fyn have also been found to be overexpressed in malign ant melanomas of Xiphophorus and may be involved in tumor progression. We report here the map location of a Xiphophorus yes gene, YES?, in L G VI, closest to the EGFR gene and the assignment of a fyn gene homolo gue to newly designated LG XV, linked to the gene for cytosolic alpha- galactosidase. We also confirmed that an EGFR-related sequence (EGFRL 1) that we previously assigned to Xiphophorus LG VI by cross-hybridiza tion to a viral erbB probe was the EGFR orthologue. Our results sugges t that the presence of expressed duplicates of members of the tyrosine kinase gene family in teleost fishes may increase the potential numbe r of targets in oncogenic cascades in fish tumor models. Mel. Carcinog . 22.150-157, 1998. (C) 1998 Wiley-Liss, Inc.