Chromosomal translocations involving paired box transcription factors in human cancer.
The PAX genes encode a family of transcription factors that control development within the neural, myogenic, lymphoid, and a variety of other lineages. These proteins are postulated to regulate expression of gene products that function in the control of cellular processes are fundamental to the development of cancer, and thus genetic alterations of these genes may contribute to neoplastic development within these lineages. In support of this premise, several PAX genes have been shown to be targets of consistent chromosomal translocations associated with specific tumor types. The t(2;13) and t(1;13) translocations associated with the myogenic soft tissue cancer alveolar rhabdomyosarcoma fuse portions of the PAX3 or PAX7 gene with a portion of the FKHR gene to generate novel fusion proteins. The t(9;14) translocation associated with the B cell tumor lymphoplasmacytoid lymphoma juxtaposes the PAX5 gene into the vicinity of the IGH locus to deregulate PAX5 expression. This review will examine the molecular basis of these translocations and the role of altered function or expression of paired box transcription factors in the process of tumorigenesis.
Barr
F G
FG
Department of Pathology, University of Pennslvania School of Medicine, Philadelphia 19104-6082, USA.
D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D000072041:PAX3 Transcription Factor; D051757:PAX5 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse