Specific integration of REV proviruses in avian bursal lymphomas

Abstract

The most common naturally occurring cancer of chickens associated with retrovirus infection is lymphoid leukosis (LL), a bursa (B) cell lymphoma. The primary causative agents are avian lymphoid leukosis viruses (LLVs), which do not necessarily have an oncogene. Recent evidence of Hayward et al.¹ suggests that LLV infection promotes the expression of a cellular gene, c-myc (homologous to the oncogene of acute leukaemia virus, MC-29) thereby triggering the transformation process. In the majority of the tumours induced by LLV, the pro virus is integrated next to the c-myc gene (refs 1,3,18,19). To examine further the specific involvement of c-myc in lymphocytic transformation, we exploited our previous findings that replication-competent or non-defective reticuloendotheliosis virus (nd REV), genetically unrelated to LLV, are also capable of inducing lymphoma in chickens, with similar latent period and pathology to LL⁵. We have characterized the structure of the nd REV proviruses in the induced tumours and report here that proviral DNA is integrated next to c-myc in over 90% of the tumours analysed. This finding strengthens the hypothesis that the c-myc and its adjacent sequences are important in B-lymphocyte transformation. We also obtained evidence that amplification and structural alteration of the chromosomal region encompassing the REV provirus and c-myc gene have occurred during tumorigenesis in some of the tumours.