Murine T lymphomas with retroviral inserts in the chromosomal 15 locus for plasmacytoma variant translocations

Abstract

The frequent trisomy of murine chromosome 15 in T lymphomas suggests that it bears one or more genes conducive to T-cell neoplasia¹. One such gene seems to be c-myc, the oncogene frequently activated in B-lymphoid tumours either by retroviral insertion, as in the avian bursal lymphomas^2,3, or by a translocation to the immunoglobulin heavy-chain locus, as in the predominant t(12; 15) of murine plasmacytomas and the analogous t(14; 8) of human Burkitt lymphomas (for reviews, see refs 1, 4–6). The c-myc gene was strongly implicated in T-cell neoplasia when 15–25% of T lymphomas arising in AKR mice, a strain prone to leukaemia, were found to have retroviral inserts near c-myc^7,8. Proviruses near c-myc were also found in several T lymphomas induced by murine leukaemia viruses (MuLV) in both mice⁹ and rats¹⁰, but many of the rat thymomas bear an insert instead at one of several other common sites^11–13, at least two of which have murine homologues on chromosome 15 (refs 14, 15). We show here that some murine T lymphomas contain proviral inserts in the recently identified chromosome 15 locus for plasmacytoma variant (6; 15) translocations, which we have denoted pvt-1 (refs 16, 17). Although 6; 15 breakpoints map cytogenetically to the same chromosome band as c-myc^18,19, the alterations of pvt-1 in tumours occur at least 72 kilobases (kb) from the c-myc promoters¹⁷. The insertions in T lymphomas suggest that an altered pvt-1 locus is conducive to neoplasia in T cells as well as B cells, possibly via long-range effects on c-myc expression.