GENETIC-DETERMINANTS OF FELINE LEUKEMIA VIRUS-INDUCED MULTICENTRIC LYMPHOMAS

Three discrete forms of feline leukemia virus (FeLV)-associated lympho ma have been described clinically: (1) thymic, (2) alimentary, and (3) multicentric. The most common and best-characterized lymphomas are of T-cell origin, generally occurring in the thymus. These tumors typica lly contain mature T-cells, involve the activation of a distinctive se t of proto-oncogenes, and contain FeLV proviruses whose long terminal repeat (LTR) sequences contain tandemly repeated enhancers. Previous s tudies of a small group of extrathymic, multicentric lymphomas implica ted a different set of genetic determinants. The present study expands those observations by examining the lineage of origin, the involvemen t of proto-oncogenes, and the structure of LTR and env gene sequences in a set of 11 natural, extrathymic lymphomas of the multicentric type . A pattern of genetic events associated with FeLV-positive multicentr ic lymphomas emerges from this analysis that is clearly distinct from the pattern associated with thymic lymphomas. The tumors do not contai n T-cells or a-cells, as evidenced by the germ line organization of TC R beta and IgH loci. Proto-oncogenes strongly implicated in T-cell lym phomagenesis are not involved in these tumors. Rather, a distinct set of proto-oncogenes may be involved. Most striking is the repeated occu rrence of an FeLV isolate whose LTR and env gene bear unique sequence elements. (C) 1995 Academic Press, Inc.