New tricks from an old oncogene: gene fusion and copy number alterations of MYB in human cancer.
MYB is a leucine zipper transcription factor that is essential for hematopoesis and for renewal of colonic crypts. There is also ample evidence showing that MYB is leukemogenic in several animal species. However, it was not until recently that clear evidence was presented showing that MYB actually is an oncogene rearranged in human cancer. In a recent study, a novel mechanism of activation of MYB involving gene fusion was identified in carcinomas of the breast and head and neck. A t(6;9) translocation was shown to generate fusions between MYB and the transcription factor gene NFIB. The fusions consistently result in loss of the 3'-end of MYB, including several highly conserved target sites for microRNAs that negatively regulate MYB expression. Deletion of these target sites may disrupt the repression of MYB, leading to overexpression of MYB-NFIB transcripts and protein and to transcriptional activation of critical MYB target genes associated with apoptosis, cell cycle control, cell growth/angiogenesis and cell adhesion. This study, together with previous and recent data showing rearrangements and copy number alterations of the MYB locus in T-cell leukemia and certain solid tumors, will be the main focus of this review.
Stenman
Göran
G
Lundberg Laboratory for Cancer Research, Department of Pathology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. goran.stenman@llcr.med.gu.se
Andersson
Mattias K
MK
Andrén
Ywonne
Y
D056915:DNA Copy Number Variations / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D050596:Oncogene Fusion / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*; D015534:Trans-Activators / Q000378:metabolism
C545202:MYB-NFIB fusion protein, human; D015514:Oncogene Proteins, Fusion; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators