| Autor: |
Melinda Varadi, Nikolett Nagy, Henning Reis, Boris Hadaschik, Christian Niedworok, Orsolya Modos, Attila Szendroi, Jason Ablat, Peter C. Black, David Keresztes, Anita Csizmarik, Csilla Olah, Nadine T. Gaisa, Andras Kiss, Jozsef Timar, Erika Toth, Erzsebet Csernak, Arpad Gerstner, Vinay Mittal, Sofia Karkampouna, Marianna Kruithof de Julio, Balazs Gyorffy, Gabor Bedics, Michael Rink, Margit Fisch, Peter Nyirady, Tibor Szarvas |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cancer Medicine, Vol 12, Iss 7, Pp 9041-9054 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2045-7634 |
| DOI: |
10.1002/cam4.5639 |
| Popis: |
Abstract Objective Administration of targeted therapies provides a promising treatment strategy for urachal adenocarcinoma (UrC) or primary bladder adenocarcinoma (PBAC); however, the selection of appropriate drugs remains difficult. Here, we aimed to establish a routine compatible methodological pipeline for the identification of the most important therapeutic targets and potentially effective drugs for UrC and PBAC. Methods Next‐generation sequencing, using a 161 cancer driver gene panel, was performed on 41 UrC and 13 PBAC samples. Clinically relevant alterations were filtered, and therapeutic interpretation was performed by in silico evaluation of drug‐gene interactions. Results After data processing, 45/54 samples passed the quality control. Sequencing analysis revealed 191 pathogenic mutations in 68 genes. The most frequent gain‐of‐function mutations in UrC were found in KRAS (33%), and MYC (15%), while in PBAC KRAS (25%), MYC (25%), FLT3 (17%) and TERT (17%) were recurrently affected. The most frequently affected pathways were the cell cycle regulation, and the DNA damage control pathway. Actionable mutations with at least one available approved drug were identified in 31/33 (94%) UrC and 8/12 (67%) PBAC patients. Conclusions In this study, we developed a data‐processing pipeline for the detection and therapeutic interpretation of genetic alterations in two rare cancers. Our analyses revealed actionable mutations in a high rate of cases, suggesting that this approach is a potentially feasible strategy for both UrC and PBAC treatments. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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