Contributions of the Gordon‐Kosswig Melanoma System to the Present Concept of Neoplasia

Abstract

Modern cancerology is based on the oncogene concept. This is rather new. The idea of the oncogene, however, is old, and can be traced back to two sources, namely to "cancer families," reported in 1866 by P. Broka, and to "virus induced" neoplasia, detected by P. Rous in 1911. A gene which is--to my knowledge--the first reported oncogene by definition was detected in the little ornamental Mexican fish Xiphophorus by Myron Gordon, Curt Kosswig, and Georg Häussler in 1928 when they observed the terrible hereditary melanomas that we are now coming to understand and to compare with other kinds of neoplasms in Xiphophorus and in mammals, including humans. Although the Xiphophorus model was always modest in its claims, it has--sometimes too early in its history--contributed many facts to the present concept of neoplasia.

Comparative structure and characterization of a CDKN2 gene in a Xiphophorus fish melanoma model

“…The ®sh genus Xiphophorus has long been established as a model organism for the study of melanoma formation (Anders, 1991;Gordon, 1931;Haussler, 1928;Kosswig, 1927;Schartl, 1995;Vielkind et al, 1989). Melanomas occur in backcross ®sh as the result of speci®c hybrid matings, thus minimizing potential environmental e ects in genetic studies.…”

“…A`two-gene' spontaneous melanoma model (which does not exclude the involvement of other loci) has been developed to explain pigment pattern enhancement and melanoma formation in hybrid ®sh constructed between the platy®sh X. maculatus and the swordtail X. helleri (Anders, 1967(Anders, , 1991Schartl, 1995;Vielkind et al, 1989). This cross has been historically named`Gordon-Kosswig' in honor of two pioneering investigators (Anders, 1991).…”

“…This cross has been historically named`Gordon-Kosswig' in honor of two pioneering investigators (Anders, 1991). When F 1 hybrids are made between the swordtail X. helleri and the platy®sh X. maculatus, the spotted dorsal (Sd) macromelanophore pigment pattern, derived from the latter species, is phenotypically enhanced.…”

“…Further enhancement of Sd occurs in backcross hybrids (to X. helleri), and nodular melanomas form in many of these latter animals. Speci®cally implicated is a sex-linked oncogene related to human epidermal growth factor receptor (called Xmrk, x-erb-B*a or Xmrk-2; Anders, 1967Anders, , 1991Schartl, 1995;Vielkind et al, 1989;Woolcock et al, 1994;Zechel et al, 1988), and an uncloned autosomal tumor suppressor locus, termed DIFF (Siciliano et al, 1976;Vielkind, 1976). Xmrk-2 has been mapped to the sex-chromosomal region harboring the macromelanophore locus (Schartl, 1990;Weis and Schartl, 1998).…”

“…According to one genetic model, it is proposed that backcross hybrids (to X. helleri) not inheriting a X. maculatus DIFF gene copy are most prone to developing melanomas (Anders, 1967(Anders, , 1991Schartl, 1995;Vielkind et al, 1989). Other genetic crosses have recently been used that similarly implicate the DIFF tumor suppressor locus (Nairn et al, 1996a,b).…”