Specific integration of REV proviruses in avian bursal lymphomas

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 ukosis 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.