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• W2054920458 abstract "Abstract Gene fusions and their chimeric products are common features of neoplasia. Given that many cancers arise by the dysregulated recapitulation of processes in normal development, we hypothesized that comparable chimeric gene products may exist in normal cells. Here, we show that a chimeric RNA, PAX3–FOXO1, identical to that found in alveolar rhabdomyosarcoma, is transiently present in cells undergoing differentiation from pluripotent cells into skeletal muscle. Unlike cells of rhabdomyosarcoma, these cells do not seem to harbor the t(2;13) chromosomal translocation. Importantly, both PAX3–FOXO1 RNA and protein could be detected in the samples of normal fetal muscle. Overexpression of the chimera led to continuous expression of MYOD and MYOG—two myogenic markers that are overexpressed in rhabdomyosarcoma cells. Our results are consistent with a developmental role of a specific chimeric RNA generated in normal cells without the corresponding chromosomal rearrangement at the DNA level seen in neoplastic cells presumably of the same lineage. Significance: A chimeric fusion RNA, PAX3–FOXO1, associated with alveolar rhabdomyosarcoma, is also present in normal non-cancer cells and tissues. Its transient expression nature and the absence of t(2;13) chromosomal translocation are consistent with a posttranscriptional mechanism. When constantly expressed, PAX3–FOXO1 interfered with the muscle differentiation process, which presumably contributes to tumorigenesis. Cancer Discov; 3(12); 1394–1403. ©2013 AACR. This article is highlighted in the In This Issue feature, p. 1317" @default.
• W2054920458 created "2016-06-24" @default.
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• W2054920458 date "2013-12-01" @default.
• W2054920458 modified "2023-10-16" @default.
• W2054920458 title "A Chimeric RNA Characteristic of Rhabdomyosarcoma in Normal Myogenesis Process" @default.
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• W2054920458 doi "https://doi.org/10.1158/2159-8290.cd-13-0186" @default.
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