Allele-specific activation of the c-myc gene in an atypical Burkitt's lymphoma carrying the t(2;8) chromosomal translocation 250 kb downstream from c-myc

Kouichi Tachibana, Nobuyuki Takayama, Koichi Matsuo, Shingo Kato, Kotaro Yamamoto, Kyoji Ohyama, Akihiro Umezawa, Toshiya Takano

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The genetic structure and regulation of the c-myc gene was comprehensively studied for the first time in Burkitt's lymphoma with t(2;8) translocation. In a Burkitt's lymphoma cell line, KOBK101, the immunoglobulin k-encoding gene on chromosome 2, accompanied by its enhancer, was translocated to the pvt-1 locus located about 250 kb downstream from c-myc on chromosome 8. Only the c-myc allele on the translocated chromosome carried aberrant SalI and KpnI sites in the first intron, so the two c-myc alleles and their transcripts were analyzed separately. The c-myc allele on the untranslocated chromosome conserved the normal c-myc sequence and was transcriptionally silent. In contrast, the c-myc allele on the translocated chromosome was actively transcribed at three- to fivefold higher levels, as compared with non-malignant B-cell lines. Additionally, it carried predominant multiple mutations consisting of 64 nucleotide substitutions, three short deletions, and a one-base insertion, most of which clustered in the first exon and intron. The 24-base deletion in the first intron completely overlapped the binding site of a putative negative transcriptional factor of the 138-kDa phosphoprotein, MIF. Thus, the multiple mutations and the deregulated, allele-specific expression of c-myc were associated with the chromosomal translocation in cis. Together activation by the long-distance immunoglobulin k enhancer, and the alleviation of negative regulation by the mutations, seemed to cause the allele-specific activation of c-myc.

Original languageEnglish
Pages (from-to)231-237
Number of pages7
JournalGene
Volume124
Issue number2
DOIs
Publication statusPublished - 1993 Feb 28

Keywords

  • Immunoglobulin K-encoding gene
  • deletion
  • enhancer
  • mutation
  • phage λ, clones
  • pvt-1 locus

ASJC Scopus subject areas

  • Genetics

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