5077

PAX3

paired box 3;PAX3;paired box 3

paired box homeotic gene 3|paired box protein Pax-3|paired domain gene 3|paired domain gene HuP2

2q35

protein-coding

Transcription factors encoded by PAX3 and PAX7 are amongst the first expressed in the embryo, being principal regulators of neurogenic and myogenic progenitor cell specification and embryonic segmentation. The basis for this review lies in the supposition that genetic programs for cell migration, thought regulated by PAX3 and PAX7 during embryonic development, become tools used by the metastatic cell. In highly metastatic neoplasms arising from cells of neurogenic and myogenic lineages such as embryonal rhabdomyosarcoma and cutaneous malignant melanoma, markedly high expression levels of PAX3 and PAX7 support this supposition. As PAX3 and PAX7 are known to play a role in the regulation of migratory events in embryogenesis, it is possible that the metastatic potential of these tumours is directly linked to migratory properties conferred them through PAX expression. Here we provide a novel perspective by correlating metastasis with expression of PAX3, PAX7 and ephrin/Eph receptors as well as NCAMs, cell surface markers normally involved in migration and adhesion during development, and propose a role for PAX genes in the increased metastatic potential of these tumours.

Transcription factors encoded by PAX3 and PAX7 are amongst the first expressed in the embryo, being principal regulators of neurogenic and myogenic progenitor cell specification and embryonic segmentation. The basis for this review lies in the supposition that genetic programs for cell migration, thought regulated by PAX3 and PAX7 during embryonic development, become tools used by the metastatic cell. In highly metastatic neoplasms arising from cells of neurogenic and myogenic lineages such as embryonal rhabdomyosarcoma and cutaneous malignant melanoma, markedly high expression levels of PAX3 and PAX7 support this supposition. As PAX3 and PAX7 are known to play a role in the regulation of migratory events in embryogenesis, it is possible that the metastatic potential of these tumours is directly linked to migratory properties conferred them through PAX expression. Here we provide a novel perspective by correlating metastasis with expression of PAX3, PAX7 and ephrin/Eph receptors as well as NCAMs, cell surface markers normally involved in migration and adhesion during development, and propose a role for PAX genes in the increased metastatic potential of these tumours.

Transcription factors encoded by PAX3 and PAX7 are amongst the first expressed in the embryo, being principal regulators of neurogenic and myogenic progenitor cell specification and embryonic segmentation. The basis for this review lies in the supposition that genetic programs for cell migration, thought regulated by PAX3 and PAX7 during embryonic development, become tools used by the metastatic cell. In highly metastatic neoplasms arising from cells of neurogenic and myogenic lineages such as embryonal rhabdomyosarcoma and cutaneous malignant melanoma, markedly high expression levels of PAX3 and PAX7 support this supposition. As PAX3 and PAX7 are known to play a role in the regulation of migratory events in embryogenesis, it is possible that the metastatic potential of these tumours is directly linked to migratory properties conferred them through PAX expression. Here we provide a novel perspective by correlating metastasis with expression of PAX3, PAX7 and ephrin/Eph receptors as well as NCAMs, cell surface markers normally involved in migration and adhesion during development, and propose a role for PAX genes in the increased metastatic potential of these tumours.

PURPOSE: In pediatric alveolar rhabdomyosarcoma, the PAX3-FOXO1 and PAX7-FOXO1 gene fusions are prognostic indicators, while little is known concerning this disease in older patients. To determine whether PAX3/7-FOXO1 fusion gene status correlates with outcome in adolescent, young adult, and adult rhabdomyosarcoma patients, the histological, immunohistochemical, and clinical characteristics of 105 patients followed at The University of Texas MD Anderson cancer Center from 1957 to 2001 were evaluated. METHODS: The samples were assembled into a tissue microarray, and fusion gene status was determined by fluorescence in situ hybridization using PAX3, PAX7, and FOXO1 loci-specific probes. The disease characteristics and specific gene fusion were correlated with patient outcomes using the log-rank test. RESULTS: Fifty-two percent of the samples exhibited a PAX3-FOXO1 fusion, 15% the PAX7-FOXO1 fusion, and 33% were negative for a rearrangement of these loci. The presence of PAX3/7-FOXO1 translocation was significantly associated with a higher frequency of metastatic disease. Although a statistically significant correlation between the PAX3/7-FOXO1 fusion gene status and overall survival was not identified, there was a trend toward better outcomes for patients with fusion-negative RMS. CONCLUSIONS: Therefore, identification of a FOXO1 fusion appears to be an interesting tool for predicting outcomes in older rhabdomyosarcoma patients and is worth further investigations in this rare subgroup of RMS population.