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  • Oncogenomics
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Functional genomic analysis reveals distinct neoplastic phenotypes associated with c-myb mutation in the bursa of Fabricius

Oncogene volume 22, pages 1073–1086 (2003)Cite this article

Abstract

Avian retroviral integration into the c-myb locus is casually associated with the development of lymphomas in the bursa of Farbricius of chickens; these arise with a shorter latency than bursal lymphomas caused by deregulation of c-myc. This study indicates that c-myb mutation in embryonic bursal precursors leads to an oligoclonal population of developing bursal follicles, showing a variable propensity to form a novel lesion, the neoplastic follicle (NF). About half of such bursas rapidly developed lymphomas. Detection of changes in gene expression, during the development of neoplasms, was carried out by cDNA microarray analysis. The transcriptional signature of lymphomas with mutant c-myb was more limited than, and only partially shared with, those of bursal lymphomas caused by Myc or Rel oncogenes. The c-myb-associated lymphomas frequently showed overexpression of c-myc and altered expression of other genes involved in cell cycle control and proliferation-related signal transduction. Oligoclonal, NF-containing bursas lacked detectable c-myc overexpression and demonstrated a pattern of gene expression distinct from that of normal bursa and partially shared with the short-latency lymphomas. This functional genomic analysis uncovered several different pathways of lymphomagenesis by oncogenic transcription factors acting in a B-cell lineage.

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Acknowledgements

The authors thank Alanna Ruddell for helpful comments and Joan Burnside, Jean-Marie Buerstedde and the Resource Center of the German Genome Project for their cooperation in obtaining cDNA clones for the microarray and subsequent analyses. This work was supported by NIH grants RO1 CA20068 to PEN and RO1 CA48746 to KLB.

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Authors and Affiliations

  1. Divisions of Basic Science and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, USA

    Paul E Neiman, Jovana J Grbiç, Robert Kimmel, Sandra J Bowers & Jeffrey Delrow

  2. Departments of Medicine and Pathology, University of Washington, Seattle, 98195, WA, USA

    Paul E Neiman

  3. Department of Biology, Johns Hopkins University, Baltimore, 21218, MD, USA

    Tatjana S Polony & Karen L Beemon

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Correspondence to Paul E Neiman.

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Neiman, P., Grbiç, J., Polony, T. et al. Functional genomic analysis reveals distinct neoplastic phenotypes associated with c-myb mutation in the bursa of Fabricius. Oncogene 22, 1073–1086 (2003). https://doi.org/10.1038/sj.onc.1206070

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