Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma.
Alveolar rhabdomyosarcoma, a malignant tumor of skeletal muscle, is characterized by a chromosomal translocation, t(2;13)(q35;q14). This translocation is associated with a structural rearrangement of the gene encoding PAX3, a presumed transcriptional regulator expressed exclusively during embryogenesis. The breakpoint results in a fusion between PAX3 and a gene provisionally named ALV, a novel member of the forkhead family of transcription factors. In PAX3-ALV, the structural integrity of both PAX3 DNA-binding regions, the paired box and homeodomain, are retained while the putative transcriptional activation domain of PAX3 is replaced by the bisected forkhead DNA-binding domain of ALV. Formation of chimeric transcription factors has now been implicated in diverse human tumors of myogenic, hematopoietic, neuroectodermal, and adipocytic origin, suggesting that transcriptional deregulation is a common mechanism of tumorigenesis.
Shapiro
D N
DN
Department of Experimental Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Sublett
J E
JE
Li
B
B
Downing
J R
JR
Naeve
C W
CW
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D012334:RNA, Neoplasm; D014157:Transcription Factors; C068686:Pax3 protein, mouse