EXPERIMENTAL FISH. Certain platyfish/swordtail hybrids are susceptible to neoplasia: some are sensitive to carcinogens, others to tumor promoters, while others develop neoplasia "spontaneously". Susceptibility to melanoma depends on an incompletely derepressed, terminally located sex chromosomal or autosomal Mendelian gene complex (Tu) composed of a pterinophore locus, 14 compartment-specific genes suppressing melanoma, a v-erbB related gene and a melanoblast determining gene (x..,R^Col-14, erbB^*a, Mel), all of which are accessory. The melanomas studied were from BC_n hybrids carrying 1 platyfish Tu in a platyfish or swordtail chromosome (interspecific tr:lnslocation), and 47 swordtail chromosomes lacking Tu. According to Southern blot, the ''transgene-like" accessory x-erbB*^a is the only platyfish-derived oncogene in the host. When x-erbB*^a was deleted, no melanomas developed.

RESULTS. x-erbB*^a is always overexpressed in the melanomas. However, melanomas also show expression of the indispensable x-erbB*ⁱ, and variable expression of x-src, x-sis, x-pdgf-r, x-ras, x-myc, x-myb and x-erbA. These genes are swordtail-derived but are apparently driven by the platyfish x-erbB*^a. Similarly, the melanomas show a 10-fold elevation of the oncogene-interrelated phosphatidylinositol (PtdIns) turnover which, for genetic reasons, must be contributed by the swordtail genome. In hybrids developing hereditary melanoma, x-src activity and Ptdlns turnover is also elevated in the brain.

Introduction of a gene that retards differentiation of stem melanoblasts prevents melanoma, but does not diminish the high x-sre activity and Ptdlns turnover in the brain.

The outgrowth of melanoma is decoupled from its preceeding biochemical processes driven by x-erbB*^a. Recouplement of these processes by cell differentiation stimulated by tumor promoters "induces" the melanoma outgrowht.

CONCLUSIONS. Many components of the melanoma machinery are apparently driven by x-erbB*^a, just as engines art controlled by an ignition system,. i.e. the initial ignition-spark and the maintenance of all ignition-timing.