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Transcriptional deregulation of myc in IgH/myc 6;7 translocation carrying rat immunocytomas

Author:
  • H Axelson
  • W S Pear
  • C K Panda
  • H Bazin
  • G Klein
  • J Sümegi
Publishing year: 1991-03
Language: English
Pages: 8-142
Publication/Series: Genes, Chromosomes and Cancer
Volume: 3
Issue: 2
Document type: Journal article
Publisher: John Wiley & Sons

Abstract english

We have previously shown that the reciprocal translocation t(6;7) associated with the spontaneous immunocytoma of the Louvain rat (RIC) leads to the juxtaposition of myc to the IgH cluster. In 10 of 14 tumors investigated the breakpoints on the myc carrying chromosome were clustered in a 1.5 kb region 5' of the intact gene, proximal to the myc promoters. In this paper we describe the effect of the translocation on myc transcription in the RIC system. Run-on analysis showed transcriptional attenuation in the normal rat myc gene, similar to the situation in mice and humans. The attenuation was almost completely abrogated in the three immunocytomas studied. Sequence analysis of two tumors failed to reveal any structural changes within exon 1, as found by others in Burkitt's lymphoma. We also show that the transcriptional initiation of myc mRNA is changed in the RICs. In an established line of rat fibroblasts (Rat-2), the more distal myc promoter (P2) is the preferred site of initiation. In RIC, however, only 30% of transcripts were initiated from P2. We found that 40% of the transcripts were initiated from P1 and 30% from a novel promoter, designated P1a, located between P1 and P2.

Keywords

  • Medical Genetics
  • Animals
  • Base Sequence
  • Burkitt Lymphoma
  • DNA Mutational Analysis
  • DNA, Neoplasm
  • Gene Expression Regulation, Neoplastic
  • Genes, Immunoglobulin
  • Genes, myc
  • Humans
  • Immunoglobulin Heavy Chains
  • Lymphoma
  • Mice
  • Molecular Sequence Data
  • Plasmacytoma
  • Promoter Regions, Genetic
  • Rats
  • Sequence Homology, Nucleic Acid
  • Species Specificity
  • Transcription, Genetic
  • Translocation, Genetic
  • Transplantation, Heterologous

Other

Published
  • ISSN: 1045-2257
Håkan Axelson
E-mail: hakan.axelson [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 34

MV 404 A31A2

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