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

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.

Telomerase reverse transcriptase expression elevated by avian leukosis virus integration in B cell lymphomas

“…Alternatively, myb may be needed for tumor initiation, but not its progression. Consistent with this, clonal proviral integrations into myb have been observed in the bursas of some of these birds (15). We hypothesize that tumorigenesis was triggered by activation of TERT by proviral integration in these four birds.…”

“…This may have provided a growth advantage to these cells, making them more susceptible to further selective mutations and malignant transformation. Conversely, myb integration sites in these four tumors were not observed by Southern blot analysis but only by direct PCR (15). This finding suggests that the myb integrations were not clonal and may represent a later event distinct from the clonal myb-lymphomas described in refs.…”

“…1C). Because these tumors had been shown to contain myb integration by nested PCR (15), these data suggested that myb integration is not clonal in these tumors. In contrast, the equal signal from the rearranged and WT allele in tumor A4 (Fig.…”

The c-Rel transcription factor and B-cell proliferation: a deal with the devil

“…Genes showing increased expression in v-Rel-transformed cells include proto-oncogenes (c-jun, c-rel), transcription factors (STAT1), cytokine receptors (IL-2Ra), growthinducing molecules (IRF-4), and antiapoptotic molecules (IAP1). Moreover, a number of genes that show increased or decreased expression in v-Rel-induced lymphoid cell tumors as compared to normal 2-week bursa have recently been identified, including several involved in adhesion, B-cell receptor signaling (through PI3 kinase), and apoptosis (Neiman et al, 2003). It is not known which induced or repressed genes are essential for transformation by v-Rel.…”

Recent Progress in Understanding Host Mucosal Response to Avian Coccidiosis and Development of Alternative Strategies to Mitigate the Use of Antibiotics in Poultry Production

“…In chickens, a limited number of low-and high-density cDNA microarrays have been developed (Morgan et al, 2001;Min et al, 2003;Neiman et al, 2003;Cogburn et al, 2004;Bliss et al, 2005 By contrast, secondary infection increased the levels of transcripts encoded by genes related to humoral immunity and reduced the levels of transcripts for the innate immune-related genes (Kim et al, 2010a). AVIELA was successfully used to compare the gene expression profiles of two B-complex disparate, genetically inbred Fayoumi chicken lines that differ in susceptibility to E. maxima (Kim et al, 2008b).…”