A Study of the myc Gene in Feline Leukaemias

I isolated and characterised a clone of the normal feline c-myc gene. Sequence analysis showed the gene to be highly related in other mammals but less well related in the chicken. The feline c-myc gene possessed an apparently non-coding first exon with a dual promoter structure, similar to that found in the human and mouse c-myc genes. The sequences of three independent FeLV v-myc genes were compared to that of the c-myc gene to identify possible structural alterations involved in myc oncogenic activation. The c-myc clone also provided probes to map c-myc rearrangements in feline thymic lymphosarcomas. Some rearrangements were due to FeLV integration within or upstream of c-myc, but one case involved a complex 3' alteration which was apparently not directly virus-induced. S1 nuclease mapping of RNA from normal cells using c-myc probes located 5' discontinuities to each of the two promoter-like sequences (P1 and P2), and a major 3' discontinuity mapping to the most 3' of two possible polyadenylation signals. Tumours carrying c-myc rearrangements did not display readily obvious abnormalities in the structure or levels of c-myc RNA, except for case T24 which appeared to contain RNA lacking exon 1 sequences. However, the ratio of P1 to P2 RNAs detected in tumours varied considerably and was high in tumours with a rearrangement adjacent to c-myc, although it was equally high in some tumours with an ostensibly normal c-myc gene structure. There was a consistent lack of detectable RNA from normal c-myc alleles in tumours containing different myc-transducing FeLVs. Also, in tumour T24 which expressed a rearranged c-myc gene, RNA from the normal c-myc allele could not be detected. The phenotype of thymic tumours was characterised with respect to expression of RNA of the a and beta-chains of the T-cell antigen receptor (TCR). Several tumours, including all those induced by two myc-transducing FeLVs and others carrying a rearranged c-myc gene, contained TCR a and beta-chain transcripts. This study provided preliminary evidence that one tumour contained independently transduced myc and beta-chain TCR genes present in separate FeLV proviruses, suggesting a direct role for TCR genes in oncogenesis