Involvement of c-myc in MuLV-induced T cell lymphomas in mice: frequency and mechanisms of activation.

In approximately 45% of the murine leukemia virus (MuLV) induced early developing T cell lymphomas in mice, integration of proviruses occurs near c-myc. From the 33 lymphomas with proviral integrations in the c-myc domain, 29 insertions were localized upstream of the first exon in a region spanning less than 2 kbp, and four integrations occurred within the first exon. In 90% of the lymphomas the transcriptional orientation of the proviruses was opposite to the transcriptional direction of c-myc. In 20% of the early T cell lymphomas, proviral integrations were detected both near c-myc and the pim-1 gene. They comprise both lymphomas in which integration near c-myc and pim-1 occurred in separate tumor cell populations, as well as tumors in which proviral integration near c-myc and pim-1 occurred in the same cell clone. Proviral integration in the c-myc domain is associated with increased myc mRNA levels (up to 30-fold). The size and nature of the c-myc mRNA precursors and processed transcripts depend on the position and orientation of the integrated proviruses.