Transcriptionally Active C-Myc Oncogene is Contained within NIARD, a DNA Sequence Associated with Chromosome Translocations in B-Cell Neoplasia
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 Cα immunoglobulin gene in various murine plasmacytomas. The mouse c-myc encoding region within NIARD spanned <2.4 kb of DNA and expressed a low level of a 2.3-kb polyadenylylated RNA in BALB/c spleen. Increased (10- to 20-fold) levels of rearranged mouse c-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 Cμ 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.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- January 1983
- DOI:
- 10.1073/pnas.80.2.519
- Bibcode:
- 1983PNAS...80..519M