Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas
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 pi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.5639 |
| _version_ | 1797838406480297984 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Melinda Varadi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T15:41:25Z |
| format | Article |
| id | doaj.art-e41fec3667254bd390a37fade443482d |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-09T15:41:25Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-e41fec3667254bd390a37fade443482d2023-04-27T10:12:44ZengWileyCancer Medicine2045-76342023-04-011279041905410.1002/cam4.5639Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomasMelinda Varadi0Nikolett Nagy1Henning Reis2Boris Hadaschik3Christian Niedworok4Orsolya Modos5Attila Szendroi6Jason Ablat7Peter C. Black8David Keresztes9Anita Csizmarik10Csilla Olah11Nadine T. Gaisa12Andras Kiss13Jozsef Timar14Erika Toth15Erzsebet Csernak16Arpad Gerstner17Vinay Mittal18Sofia Karkampouna19Marianna Kruithof de Julio20Balazs Gyorffy21Gabor Bedics22Michael Rink23Margit Fisch24Peter Nyirady25Tibor Szarvas26Department of Urology Semmelweis University Budapest HungaryDepartment of Urology Semmelweis University Budapest HungaryDr. Senckenberg Institute of Pathology University Hospital Frankfurt, Goethe University Frankfurt Frankfurt GermanyDepartment of Urology, West German Cancer Center University of Duisburg‐Essen, University Hospital Essen Essen GermanyDepartment of Urology, West German Cancer Center University of Duisburg‐Essen, University Hospital Essen Essen GermanyDepartment of Urology Semmelweis University Budapest HungaryDepartment of Urology Semmelweis University Budapest HungaryVancouver Prostate Centre University of British Columbia Vancouver CanadaVancouver Prostate Centre University of British Columbia Vancouver CanadaDepartment of Urology Semmelweis University Budapest HungaryDepartment of Urology Semmelweis University Budapest HungaryDepartment of Urology, West German Cancer Center University of Duisburg‐Essen, University Hospital Essen Essen GermanyInstitute of Pathology RWTH Aachen University Aachen GermanyDepartment of Pathology, Forensic and Insurance Medicine Semmelweis University Budapest HungaryDepartment of Pathology, Forensic and Insurance Medicine Semmelweis University Budapest HungaryNational Institute of Oncology Budapest HungaryNational Institute of Oncology Budapest HungaryThermo Fisher Scientific Ann Arbor Michigan USAThermo Fisher Scientific Ann Arbor Michigan USADepartment for BioMedical Research, Urology Research Laboratory University of Bern Bern SwitzerlandDepartment for BioMedical Research, Urology Research Laboratory University of Bern Bern SwitzerlandResearch Centre for Natural Sciences, Cancer Biomarker Research Group Institute of Enzymology Budapest HungaryDepartment of Pathology and Experimental Cancer Research Semmelweis University Budapest HungaryDepartment of Urology University Medical Center Hamburg‐Eppendorf Hamburg GermanyDepartment of Urology University Medical Center Hamburg‐Eppendorf Hamburg GermanyDepartment of Urology Semmelweis University Budapest HungaryDepartment of Urology Semmelweis University Budapest HungaryAbstract 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.https://doi.org/10.1002/cam4.5639molecular geneticsOncomineprimary bladder adenocarcinomatargeted therapyurachal cancer |
| spellingShingle | 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 Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas Cancer Medicine molecular genetics Oncomine primary bladder adenocarcinoma targeted therapy urachal cancer |
| title | Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas |
| title_full | Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas |
| title_fullStr | Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas |
| title_full_unstemmed | Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas |
| title_short | Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas |
| title_sort | clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas |
| topic | molecular genetics Oncomine primary bladder adenocarcinoma targeted therapy urachal cancer |
| url | https://doi.org/10.1002/cam4.5639 |
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