Functional genomic analysis reveals distinct neoplastic phenotypes associated with c-myb mutation in the bursa of Fabricius.
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.
Neiman
Paul E
PE
Divisions of Basic Science and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. pneiman@fhere.org
Grbiç
Jovana J
JJ
Polony
Tatjana S
TS
Kimmel
Robert
R
Bowers
Sandra J
SJ
Delrow
Jeffrey
J
Beemon
Karen L
KL
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002060:Bursa of Fabricius / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics*; D003673:Defective Viruses / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020570:Genes, myb; D016259:Genes, myc; D020573:Genes, rel; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors
D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc