Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas
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...
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2021
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oai:doaj.org-article:8578a14c3d6944a6908e1aad77edec192021-11-11T17:02:52ZDeciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas10.3390/ijms2221115641422-00671661-6596https://doaj.org/article/8578a14c3d6944a6908e1aad77edec192021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11564https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Adult 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 <i>CDH1</i>, <i>SLUG</i>, <i>MMP9</i>, <i>RAB22a</i>, <i>S100P,</i> and <i>LAPTM4b</i>, 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 <i>RAB3IP-HMGA2</i> in frame gene rearrangement and <i>FGFR4</i> mutation; microsatellite instability analysis did not detect any alteration. In silico analysis confirmed the mutation of <i>FGFR4</i> 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.Alessandro De VitaSilvia VanniValentina FaustiClaudia CocchiFederica RecineGiacomo MiserocchiChiara LiveraniChiara SpadazziMassimo BassiManlio GessaroliAngelo CampobassiGiovanni De LucaFederica PieriAnna FarnediEugenia FranchiniAnna FerrariChiara DomizioEnrico CavagnaLorena GurrieriAlberto BongiovanniNada RivaSebastiano CalponaGiandomenico Di MennaSilvia Angela DebonisToni IbrahimLaura MercataliMDPI AGarticleadult rhabdomyosarcomaprimary culturegene expression profilingchemotherapy3D collagen-based scaffold culture systemsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11564, p 11564 (2021) |
| institution |
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| collection |
DOAJ |
| language |
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| topic |
adult rhabdomyosarcoma primary culture gene expression profiling chemotherapy 3D collagen-based scaffold culture systems Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
adult rhabdomyosarcoma primary culture gene expression profiling chemotherapy 3D collagen-based scaffold culture systems Biology (General) QH301-705.5 Chemistry QD1-999 Alessandro De Vita Silvia Vanni Valentina Fausti Claudia Cocchi Federica Recine Giacomo Miserocchi Chiara Liverani Chiara Spadazzi Massimo Bassi Manlio Gessaroli Angelo Campobassi Giovanni De Luca Federica Pieri Anna Farnedi Eugenia Franchini Anna Ferrari Chiara Domizio Enrico Cavagna Lorena Gurrieri Alberto Bongiovanni Nada Riva Sebastiano Calpona Giandomenico Di Menna Silvia Angela Debonis Toni Ibrahim Laura Mercatali Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas |
| description |
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 <i>CDH1</i>, <i>SLUG</i>, <i>MMP9</i>, <i>RAB22a</i>, <i>S100P,</i> and <i>LAPTM4b</i>, 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 <i>RAB3IP-HMGA2</i> in frame gene rearrangement and <i>FGFR4</i> mutation; microsatellite instability analysis did not detect any alteration. In silico analysis confirmed the mutation of <i>FGFR4</i> 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. |
| format |
article |
| author |
Alessandro De Vita Silvia Vanni Valentina Fausti Claudia Cocchi Federica Recine Giacomo Miserocchi Chiara Liverani Chiara Spadazzi Massimo Bassi Manlio Gessaroli Angelo Campobassi Giovanni De Luca Federica Pieri Anna Farnedi Eugenia Franchini Anna Ferrari Chiara Domizio Enrico Cavagna Lorena Gurrieri Alberto Bongiovanni Nada Riva Sebastiano Calpona Giandomenico Di Menna Silvia Angela Debonis Toni Ibrahim Laura Mercatali |
| author_facet |
Alessandro De Vita Silvia Vanni Valentina Fausti Claudia Cocchi Federica Recine Giacomo Miserocchi Chiara Liverani Chiara Spadazzi Massimo Bassi Manlio Gessaroli Angelo Campobassi Giovanni De Luca Federica Pieri Anna Farnedi Eugenia Franchini Anna Ferrari Chiara Domizio Enrico Cavagna Lorena Gurrieri Alberto Bongiovanni Nada Riva Sebastiano Calpona Giandomenico Di Menna Silvia Angela Debonis Toni Ibrahim Laura Mercatali |
| author_sort |
Alessandro De Vita |
| title |
Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas |
| title_short |
Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas |
| title_full |
Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas |
| title_fullStr |
Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas |
| title_full_unstemmed |
Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas |
| title_sort |
deciphering the genomic landscape and pharmacological profile of uncommon entities of adult rhabdomyosarcomas |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/8578a14c3d6944a6908e1aad77edec19 |
| work_keys_str_mv |
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