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

• DOI: 10.1073/pnas.80.2.519
• Publication Date: 2006-05-31T09:14:10Z
• Authors: Kenneth B. Marcu; Linda J. Harris; Lawrence W. Stanton; Jan Erikson; Rosemary Watt; Carlo M. Croce
• Keywords: Transcription, Genetic; 610; Biochemistry; Translocation, Genetic; Mice; 03 medical and health sciences; 0302 clinical medicine; Metabolism:; 616; Animals; Humans; RNA, Messenger; Strains: BALB/C; Mice, Inbred BALB C; Base Sequence; DNA Restriction Enzymes; Neoplasms, Experimental; Oncogenes; Burkitt Lymphoma; Organs:; 3. Good health; Liver; Cellular Biology:; RNA; Hereditary Factors:; Poly A; Spleen; Transplantable Tumors: MPC (ALL); Plasmacytoma

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 <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 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.