Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma

• Published in: Cancer research (Chicago, Ill.) Vol. 53; no. 21; pp. 5108 - 5112
• Main Authors: SHAPIRO, D. N, SUBLETT, J. E, BAITAO LI, DOWNING, J. R, NAEVE, C. W
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-11-1993
• Subjects: ALV gene; Amino Acid Sequence; Base Sequence; binding; Biological and medical sciences; Cell Line; Chromosome Mapping; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 2; Cloning, Molecular; Conserved Sequence; Diseases of the osteoarticular system; DNA; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; domains; gene fusion; genes; homeodomains; Humans; man; Medical sciences; Molecular Sequence Data; Paired Box Transcription Factors; PAX3 gene; PAX3 Transcription Factor; rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar - genetics; Rhabdomyosarcoma, Alveolar - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - isolation & purification; Sequence Homology, Amino Acid; transcription factors; Transcription Factors - biosynthesis; Transcription Factors - genetics; Translocation, Genetic; Tumor Cells, Cultured; Tumors of striated muscle and skeleton; Chromosomal aberration; Human; Breakpoint; Pathogenesis; Exploration; Malignant tumor; Striated muscle disease; Established cell line; Gene rearrangement; Abnormal chromosome; Abnormal A2 chromosome; Transcription factor; Abnormal D13 chromosome; Alveolar rhabdomyosarcoma; Chromosome translocation
• ISSN: 0008-5472; 1538-7445

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.