The 15;12 chromosome translocation in murine plasmacytomas and the 8;14 in human Burkitt lymphomas often link the cellular myc oncogene to the locus for constant regions of immunoglobulin heavy chains (CH locus). To clarify how and why c‐myc translocation occurs, we have sequenced the mouse and human c‐myc genes and correlated c‐myc transcription with c‐myc rearrangement. Both genes comprise three exons; the second and third encode the myc polypeptide, which is conserved between mammals and birds, particularly in its more basic C‐terminal half. Southern blots showed that four of 12 Burkitt lines have c‐myc linked near CH switch regions and two near the joining region (JH) locus. Hence, immunoglobulin recombination machinery may participate in translocation, although the common myc breakpoint region around exon 1 does not resemble a switch region. Tumours with breakpoints just 5′ to exon 1, or distant from c‐myc, had normal c‐myc mRNAs of 2.25 and 2.4 kb, which differ at their 5′ ends, while tumours with breakpoints within exon 1 or intron 1 had altered c‐myc mRNAs (2.1‐2.7 kb in Burkitt lines), initiated within intron 1. Both types of mRNAs probably yield the same polypeptide. Since the untranslocated c‐myc allele was generally silent, translocation to the CH locus must induce constitutive c‐myc expression. The presence of c‐myc mRNA in immortal but non‐tumorigenic lymphoblastoid cell lines may implicate c‐myc in an immortalization step.

Molecular cloning has recently established that the 15;12 chromosome translocations in murine plasmacytomas fuse DNA from chromosome 15 to the immunoglobulin heavy (H) chain locus, usually within the switch recombination region near the a constant region gene. We show here that the incoming DNA bears the cellular gene (c-myc) homologous to the oncogene (vnmyc) of avian retrovirus MC29. In human Burkitt lymphomas bearing an 8;14 translocation, c-myc was also rearranged, apparently (in at least two cases) to an H chain switch recombination region (IA or a), and both products of a reciprocal chro-

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The variant (6;15) translocations in murine plasmacytomas join the myc oncogene‐bearing band of chromosome 15 and the immunoglobulin kappa band of chromosome 6. We recently cloned a region from chromosome 15 linked to C kappa and have now used probes from that region to define the major locus of plasmacytoma variant translocations, which we denote pvt‐1. In five of nine plasmacytomas we analysed, the 6;15 translocation resulted from reciprocal recombination between the C kappa locus and a 4.5‐kb region of pvt‐1. Moreover, nearby we located the region shown by others to have undergone a complex (15;12;6) translocation in plasmacytoma PC7183. All the chromosome 6 breakpoints fell between 1 and 3 kb 5′ to C kappa but only two were near J kappa genes. Thus the J kappa ‐C kappa region appears to be a recombination ‘hot spot’ in lymphocytes, but the breaks are unlikely to be mediated via V/J recombination enzymes. Comparison of a cloned 108‐kb region across pvt‐1 and another of 52 kb across c‐myc established that the pvt‐1 breakpoints lie at least 72 kb from the c‐myc promoters. Since c‐myc is expressed at a substantial level, the 6;15 translocation apparently activates c‐myc. Activation may occur directly, at a remarkable distance along the chromosome, or indirectly, via a putative pvt‐1 gene product.

In chronic myeloid leukemia and some cases of acute lymphoblastic leukemia, a 9;22 chromosome translocation has fused most of the c-abl oncogene to a gene designated bcr. To explore in vivo the biological effects of the chimeric gene, we introduced a facsimile of the translocation product, a bcr-v-abl gene, into the mouse germ line under the control of the immunoglobulin heavy-chain enhancer or a retroviral long terminal repeat. Some transgenic mice bearing either construct developed clonal lymphoid tumors. T lymphomas predominated, but some pre-B lymphomas developed. The transgenes were expressed in the tumors but not detectably in the lymphoid tissues of nontumorous transgenic animals, implying that transcription is activated by a low-frequency somatic event. These results demonstrate that bcr-v-abl is tumorigenic in vivo and provide a new animal model for lymphomagenesis.