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Localization of a CDKN2 gene in linkage group V of Xiphophorus fishes defines it as a candidate for the DIFF tumor suppressor
Author(s) -
Kazianis Steven,
Gutbrod Heidrun,
Nairn Rodney S.,
McEntire Brenda B.,
Coletta Luis Della,
Walter Ronald B.,
Borowsky Richard L.,
Woodhead Avril D.,
Setlow Richard B.,
Schartl Manfred,
Morizot Donald C.
Publication year - 1998
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199807)22:3<210::aid-gcc6>3.0.co;2-z
Subject(s) - xiphophorus , biology , genetics , locus (genetics) , cdkn2a , gene , melanoma , suppressor , hybrid , tumor suppressor gene , candidate gene , genotype , genetic linkage , carcinogenesis , fish <actinopterygii> , botany , fishery
The Xiphophorus hybrid melanoma model represents one of the earliest reported cases of genetically regulated tumor susceptibility. Melanoma formation in Xiphophorus hybrids may be explained by the inheritance of two genes: a sex‐linked oncogene, Xmrk, and a putative tumor suppressor locus, termed DIFF, located in Linkage Group V (LG V). Several genetic mapping procedures were used to produce a new Xiphophorus LG V map with 20 loci. All markers, particularly a recently cloned Xiphophorus CDKN2 gene family member, called CDKN2X, were tested for associations of genotype with degree of macromelanophore pigment pattern modification and susceptibility to melanoma formation in backcross hybrids of seven genetic types, involving 1,110 fish and three pigment patterns. Highly significant associations of CDKN2X genotypes with such phenotypic effects suggests that this gene is a strong candidate for the classically defined DIFF tumor suppressor gene. Because published results have documented the involvement of the CDKN2A ( p16, MTS1, and INK4A ) tumor suppressor gene in human melanoma formation, the possibility of CDKN2 genes acting as tumor suppressors in both man and Xiphophorus is likely. Genes Chromosomes Cancer 22:210–220, 1998. © 1998 Wiley‐Liss, Inc.