A common region for proviral DNA integration in MoMuLV-induced rat thymic lymphomas

Abstract

Similarly to other mammalian and avian retroviruses that lack a transforming gene1, moloney murine leukaemia virus (MoMuLV) causes no morphological transformation in infected tissue culture cells. However, following injection in an appropriate animal host, MoMuLV induces mainly thymic lymphomas after a long latency period2,3. A common characteristic of neoplasms induced by retroviruses lacking transforming genes is their clonal origin4–9. Here we have generated MoMuLV-induced rat thymic lymphomas and confirmed their clonal nature. Furthermore, we took advantage of the clonality of these tumours to investigate the specificity of provirus integration in the tumour DNA. We reasoned that if several independently derived thymic lymphomas would contain the provirus integrated in the same region of cellular DNA, this would be a strong indication that this integration event is a contributing factor in oncogenesis. The results indicate that there is indeed a cellular DNA region (termed the ML VI-1 locus) that serves as the substrate for proviral DNA integration in 5 out of 16 tumours we examined.