Analysis of gene expression during myc oncogene-induced lymphomagenesis inthe bursa of Fabricius

The transcriptional effects of deregulated myc gene overexpression are impl icated in tumorigenesis in a spectrum of experimental and naturally occurri ng neoplasms. In follicles of the chicken bursa of Fabricius, myc induction of B-cell neoplasia requires a target cell population present during early bursal development and progresses through preneoplastic transformed follic les to metastatic lymphomas. We developed a chicken immune system cDNA micr oarray to analyze broad changes in gene expression that occur during: norma l embryonic B-cell development and during myc-induced neoplastic transforma tion in the bursa. The number of mRNAs showing at least 3-fold change was g reater during myc-induced lymphomagenesis than during normal development, a nd hierarchical cluster analysis of expression patterns revealed that level s of several hundred mRNAs varied in concert with levels of myc overexpress ion, A set of 41 mRNAs were most consistently elevated in myc-overexpressin g preneoplastic and neoplastic cells, most involved in processes thought to be subject to regulation by Myc. The mRNAs for another cluster of genes we re overexpressed in neoplasia independent of myc expression level, includin g a small subset with the expression signature of embryonic bursal lymphocy tes. Overexpression of myc, and some of the genes overexpressed with myc, m ay be important for generation of preneoplastic transformed follicles. Howe ver, expression profiles of late metastatic tumors showed a large variation in concert with myc expression levels, and some showed minimal myc overexp ression. Therefore, high-level myc overexpression may be more important in the early induction of these lymphomas than in maintenance of late-stage me tastases.