ACTIVATION OF THE C-MYC ONCOGENE BY THE IMMUNOGLOBULIN HEAVY-CHAIN GENE ENHANCER AFTER MULTIPLE SWITCH REGION-MEDIATED CHROMOSOME REARRANGEMENTS IN A MURINE PLASMACYTOMA
ACTIVATION OF THE C-MYC ONCOGENE BY THE IMMUNOGLOBULIN HEAVY-CHAIN GENE ENHANCER AFTER MULTIPLE SWITCH REGION-MEDIATED CHROMOSOME REARRANGEMENTS IN A MURINE PLASMACYTOMA
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DOI：
10.1073/pnas.82.11.3746
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
KLEIN, G
中科院分区：
文献类型：
--
作者：
FAHRLANDER, PD;SUMEGI, J;KLEIN, G
Presented is a detailed molecular analysis of the rearranged c-myc oncogene from ABPC45, an unusual plasmacytoma that was originally classified as translocation-negative. Previous data obtained by high-resolution chromosome banding suggested that this tumor was a member of a small group distinguished by the absence of rcpt (12;15) or (6;15) and further characterized by a band deletion near the c-myc locus on chromosome 15. However, genomic Southern blotting and analysis of the cloned oncogene reveal the following: chromosome 12 sequences lie 365 base pairs 5'' of the rearranged c-myc; this DNA consists of Ig .alpha. switch region and 5'' Ig .mu. switch region sequences rearranged in an aberrant fashion; and the Ig H-chain gene enhancer element now resides .apprxeq. 2.5 kilobase pairs 5'' of c-myc. The rearrangement of c-myc in ABPC45 evidently occurred via a multistep switch region-mediated process. A reciprocal translocation has indeed taken place. Unlike many other plasmacytomas, this event did not interrupt the normal c-myc transcription unit. Disruption of gene regulation is manifested in part by a change in relative usage of the 2 promoters normally used by the unrearranged gene. In contrast to several of its counterparts in Burkitt lymphomas, DNA sequence analysis of the translocated c-myc gene of APBC45 reveals that it has not acquired point mutations in the noncoding 1st exon. A cis-acting regulatory element normally located 5'' of exon 1 apparently is lost. H-chain constant region or enhancer sequences exert similar cis effects on translocated c-myc loci.
