Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas
| Autor: | Chiara Spadazzi, Laura Mercatali, Chiara Liverani, Lorena Gurrieri, Sebastiano Calpona, Anna Maria Ferrari, Giandomenico Di Menna, Federica Pieri, Chiara Domizio, Toni Ibrahim, Enrico Cavagna, Angelo Campobassi, Alessandro De Vita, Valentina Fausti, Nada Riva, Giovanni De Luca, Silvia Angela Debonis, Federica Recine, Anna Farnedi, Eugenia Franchini, Manlio Gessaroli, Claudia Cocchi, Giacomo Miserocchi, Silvia Vanni, Massimo Bassi, Alberto Bongiovanni |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Epithelial-Mesenchymal Transition QH301-705.5 In silico Soft Tissue Neoplasms medicine.disease_cause chemotherapy Article Catalysis CDH1 Inorganic Chemistry LAPTM4B Rhabdomyosarcoma Biomarkers Tumor medicine gene expression profiling Humans Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy Aged Mutation primary culture biology Organic Chemistry Microsatellite instability Sarcoma Genomics General Medicine Gene rearrangement medicine.disease Up-Regulation Computer Science Applications Gene expression profiling Chemistry 3D collagen-based scaffold culture systems Cancer research biology.protein Female Microsatellite Instability Microsatellite Instability Analysis adult rhabdomyosarcoma |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 11564, p 11564 (2021) International Journal of Molecular Sciences Volume 22 Issue 21 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of all soft tissue sarcomas (STS). Consequently, the natural history and the clinical management of this disease are infrequently reported. In order to fill this gap, we investigated the molecular biology of an adult RMS case series. The expression of epithelial mesenchymal transition-related gene and chemoresistance-related gene panels were evaluated. Moreover, taking advantage of our STS translational model combining patient-derived primary culture and 3D-scaffold, the pharmacological profile of an adult head and neck sclerosing RMS was assessed. Furthermore, NGS, microsatellite instability, and in silico analyses were carried out. RT-PCR identified the upregulation of CDH1, SLUG, MMP9, RAB22a, S100P, and LAPTM4b, representing promising biomarkers for this disease. Pharmacological profiling showed the highest sensitivity with anthracycline-based regimen in both 2D and 3D culture systems. NGS analysis detected RAB3IP-HMGA2 in frame gene rearrangement and FGFR4 mutation microsatellite instability analysis did not detect any alteration. In silico analysis confirmed the mutation of FGFR4 as a promising marker for poor prognosis and a potential therapeutic target. We report for the first time the molecular and pharmacological characterization of rare entities of adult head and neck and posterior trunk RMS. These preliminary data could shed light on this poorly understood disease. |
| Databáze: | OpenAIRE |
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