The consistent appearance of specific chromosomal translocations in human Burkitt lymphomas and murine plasmacytomas has suggested that these translocations might play a role in malignant transformation. Here we show that transformation of these cells is frequently accompanied by the somatic rearrangement of a cellular analogue of an avian retrovirus transforming gene, c-myc. Moreover, we map c-myc to human chromosome 8 band q24, the chromosomal segment involved in the reciprocal Burkitt translocations [t(8;14), t(8;22), and t(2;8)]. In two t(8;14) human Burkitt cell lines, c-myc appears to have been translocated directly into a DNA restriction fragment that also encodes the immunoglobulin ,u chain gene. In the case of a specific cloned fragment of DNA derived from a mouse plasmacytoma, we demonstrate directly that c-myc has been translocated into the immunoglobulin a switch region. Our data provide a molecular basis for considering the role that specific translocations might play in malignant transformation.

A transforming gene isolated from T24 human bladder carcinoma cells is closely related to the BALB murine sarcoma virus (MSV) onc gene (v-bas). This transforming gene is localized to a 4.6 kilobase pair (kbp) region and is expressed as a 1.2-kbp polyadenylated transcript, which contains v-bas related sequences. Moreover, antisera known to detect the immunologically related onc gene products of BALB- and Harvey-MSVs recognized elevated levels of a related protein in T24 cells. The normal human homologue of v-bas was found to be indistinguishable from the T24 oncogene by heteroduplex and restriction enzyme analysis. These results imply that rather subtle genetic alterations have led to the activation of the normal human homologue of v-bas as a human transforming gene.

Total cellular poly(A)-enriched RNA from.a variety of fresh human leukemic blood cells and hematopoietic cell lines was analyzed for homology with molecularly cloned DNA probes containing the one sequence of Abelson. murine leukemia virus (Ab-MuLV), Harvey murine sarcoma virus (Ha-MuSV), simian sarcoma virus (SSV), and avian myelocytomatosis virus strain MC29. Results with the fresh blood cells paralleled those obtained with the cell lines. With Ab-MuLV and Ha,-MuSV, multiple RNA bands were visualized in all cell types examined without significant variation in the relative intensities of the bands. When SSV was used as the probe, expression of related one sequences was absent in all of the hematopoietic cell types examined except for one neoplastic T-cell line (HUT 102), which produces the human T-cell leukemia (lymphoma) retrovirus HTLV. In this cell line, a single band (4.2 kilobases) was -observed. With MC29 as the probe, a single band of 2.7 kilobases was visualized in all cell types examined with only a 1-to 2-fold-variation in intensity-of hybridization. An exception was the promyelocytic cell line, HL60, which expressed approximately 10-fold more MC29-related one sequences. With induction of differentiation of HL60 with either dimethyl sulfoxide or retinoic acid, a marked diminution in the amount of the MC29-related, but not the Ab-MuLV-related, onc message was observed.

Polyadenylated RNAs of certain human tumour cell lines are shown to contain transcripts related to the cell-derived transforming onc genes of molecularly cloned primate, murine or avian transforming retrovirus genomes. Thus, analogues of retroviral transforming genes are both present and frequently expressed in human neoplastic cells.