v-erbB related sequences in Xiphophorus that map to melanoma determining Mendelian loci and overexpress in a melanoma cell line.

Certain genotypes of Xiphophorus harbour an accessory Mendelian gene which following loss, impairment, or insufficiency of its regulatory genes in the germ line, mediates the hereditary capacity to develop neoplasia spontaneously or following induction with initiating and promoting carcinogens. Together with its linked regulatory genes it forms a 'tumor gene-complex' (Tu-complex). We concentrated on accessory sex chromosomal Tu-complexes that are responsible for sex chromosome-linked melanoma formation. Southern analyses of the xiphophorine genome with 15 authentic oncogene probes revealed so far that only three v-erbB related EcoRI fragments comprising 4.9 kb of a certain X-, 11.5 kb of another X-, and 6.7 kb of both a Y- and Z-chromosome are inherited in parallel with the Tu-complex and melanoma formation. They are accessory in the genome, and are highly homologous with each other. The sequence of the X-chromosomal 4.9 kb fragment shows minor but significant differences to that of the invariably present autosomal xiphophorine erbB (x-erbB) fragment of 5.5 kb, indicating that at least two different x-erbB genes coding for different EGF receptors can exist in the fish. Northern analyses showed expression of both genes in a fibroblast cell line, and overexpression of the sex chromosomal x-erbB in a melanoma cell line. The co-segregation of the hereditary trait of melanoma with the sex chromosomal x-erbB fragments, suggests that the accessory x-erbB gene may be responsible for the switch from the normal to the neoplastic state of the pigment cells.