Transcriptionally active c- myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia

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Abstract
NIARD (non-immunoglobulin-associated rearranging DNA) is located on mouse chromosome 15 at the break point of a commonly observed translocation event involving chromosomes 15 and 12 in murine plasmacytomas. The human cellular analogue of the v- myc oncogene of avian myelocytomatosis virus, strain MC-29, is known to reside on the distal end of human chromosome 8 and has been observed to translocate to chromosome 14 in Burkitt lymphomas. Using a cDNA clone specific for the transcript of the human c- myc gene (H c- myc ), we show that the mouse c- myc (M c- myc ) gene is contained within NIARD. NIARD-associated chromosome translocations occurred 1.3-2 kilobases (kb) 5′ of the mouse c- myc gene where NIARD recombines with the switch region of the C α immunoglobulin gene in various murine plasmacytomas. The mouse c- myc encoding region within NIARD spanned myc transcripts (i.e., ≈1.8-2.1 kb) were observed in plasmacytomas that have NIARD-associated chromosome translocations. Human c- myc and NIARD probes detected DNA rearrangements of human c- myc in four of seven Burkitt lymphomas. DNA sequences adjacent to the human c- myc gene recombined with the C μ immunoglobulin gene locus on chromosome 14 in several Burkitt lymphomas. The activation of the c- myc oncogene by chromosome translocation implicates its involvement in B-cell oncogenesis.