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

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Abstract
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.

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