C-myc activation in an unusual retrovirus-induced avian T-lymphoma resembling Marek's disease: Proviral insertion 5' of exon one enhances the expression of an intron promoter

Characterization of nonacute retrovirus-induced neoplasms have greatly facilitated our understanding of the mechanisms by which host protooncogenes are activated. Here we report the molecular characterization of a newly identified chicken lymphoma, which does not involve the bursa of Fabricius. This lymphoma, specifically induced by reticuloendotheliosis virus (REV), is similar in tumor location and T-cell origin to Marek's disease, a herpesvirus-induced T-lymphoma. We show the c-myc is the specific target locus for REV insertion. Integrated proviruses are all located upstream of the c-myc coding exons, and 60% are 5' to the first noncoding exon. One-half of the proviruses are oriented in the opposite transcriptional direction as the c-myc gene. This insertion pattern is in contrast to the pattern in B-lymphomas induced by the same virus. While some of the proviruses in these T-lymphomas used the 3' LTR promoter to transcribe the downstream c-myc gene, others apparently activated a common, cryptic promoter located in the first intron. To our knowledge, this is the first molecular description of an avian T-lymphoma induced by a nonacute retrovirus.