Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas
Cancer Medicine, vol. 12, pp. 9041–9054
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.
Authors 26
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Affiliation as printed
Department of Urology Semmelweis University Budapest Hungary
Department of Urology, Semmelweis University, Budapest, Hungary
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Affiliation as printed
Department of Urology Semmelweis University Budapest Hungary
Department of Urology, Semmelweis University, Budapest, Hungary
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Goethe University Frankfurt · Essen University Hospital · University Hospital Frankfurt · University of Duisburg-Essen
Affiliation as printed
Dr. Senckenberg Institute of Pathology University Hospital Frankfurt, Goethe University Frankfurt Frankfurt Germany
Institute of Pathology, West German Cancer Center University of Duisburg‐Essen, University Hospital Essen Essen Germany
Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany
Institute of Pathology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
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Essen University Hospital · University of Duisburg-Essen
Affiliation as printed
Department of Urology, West German Cancer Center University of Duisburg‐Essen, University Hospital Essen Essen Germany
Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
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Essen University Hospital · University of Duisburg-Essen
Affiliation as printed
Department of Urology, West German Cancer Center University of Duisburg‐Essen, University Hospital Essen Essen Germany
Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
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Affiliation as printed
Department of Urology Semmelweis University Budapest Hungary
Department of Urology, Semmelweis University, Budapest, Hungary
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Affiliation as printed
Department of Urology Semmelweis University Budapest Hungary
Department of Urology, Semmelweis University, Budapest, Hungary
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University of British Columbia · Vancouver Prostate Centre
Affiliation as printed
Vancouver Prostate Centre University of British Columbia Vancouver Canada
Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada
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University of British Columbia · Vancouver Prostate Centre
Affiliation as printed
Vancouver Prostate Centre University of British Columbia Vancouver Canada
Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada
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Affiliation as printed
Department of Molecular Biology Institute of Biochemistry and Molecular Biology, Semmelweis University Budapest Hungary
Department of Urology Semmelweis University Budapest Hungary
Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary
Department of Urology, Semmelweis University, Budapest, Hungary
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Affiliation as printed
Department of Urology Semmelweis University Budapest Hungary
Department of Urology, Semmelweis University, Budapest, Hungary
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Essen University Hospital · University of Duisburg-Essen
Affiliation as printed
Department of Urology, West German Cancer Center University of Duisburg‐Essen, University Hospital Essen Essen Germany
Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
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Affiliation as printed
Institute of Pathology RWTH Aachen University Aachen Germany
Institute of Pathology, RWTH Aachen University, Aachen, Germany
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Affiliation as printed
Department of Pathology, Forensic and Insurance Medicine Semmelweis University Budapest Hungary
Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
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Affiliation as printed
Department of Pathology, Forensic and Insurance Medicine Semmelweis University Budapest Hungary
Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
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National Institute of Oncology
Affiliation as printed
National Institute of Oncology Budapest Hungary
National Institute of Oncology, Budapest, Hungary
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National Institute of Oncology
Affiliation as printed
National Institute of Oncology Budapest Hungary
National Institute of Oncology, Budapest, Hungary
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Thermo Fisher Scientific (United States)
Affiliation as printed
Thermo Fisher Scientific Ann Arbor Michigan USA
Thermo Fisher Scientific, Ann Arbor, Michigan, USA
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Affiliation as printed
Department for BioMedical Research, Urology Research Laboratory University of Bern Bern Switzerland
Department for BioMedical Research, Urology Research Laboratory, University of Bern, Bern, Switzerland
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University of Bern · University Hospital of Bern
Affiliation as printed
Department for BioMedical Research, Urology Research Laboratory University of Bern Bern Switzerland
Department of Urology, Inselspital Bern University Hospital Bern Switzerland
Department for BioMedical Research, Urology Research Laboratory, University of Bern, Bern, Switzerland
Department of Urology, Inselspital, Bern University Hospital, Bern, Switzerland
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Semmelweis University · Institute of Molecular Life Sciences · HUN-REN Research Centre for Natural Sciences
Affiliation as printed
2nd Department of Pediatrics and Department of Bioinformatics Semmelweis University Budapest Hungary
Research Centre for Natural Sciences, Cancer Biomarker Research Group Institute of Enzymology Budapest Hungary
2nd Department of Pediatrics and Department of Bioinformatics, Semmelweis University, Budapest, Hungary
Research Centre for Natural Sciences, Cancer Biomarker Research Group, Institute of Enzymology, Budapest, Hungary
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Affiliation as printed
Department of Pathology and Experimental Cancer Research Semmelweis University Budapest Hungary
Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
Department of Urology University Medical Center Hamburg‐Eppendorf Hamburg Germany
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
Department of Urology University Medical Center Hamburg‐Eppendorf Hamburg Germany
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Affiliation as printed
Department of Urology Semmelweis University Budapest Hungary
Department of Urology, Semmelweis University, Budapest, Hungary
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Tibor Szarvas corresponding
Semmelweis University · Essen University Hospital · University of Duisburg-Essen
Affiliation as printed
Department of Urology Semmelweis University Budapest Hungary
Department of Urology, West German Cancer Center University of Duisburg‐Essen, University Hospital Essen Essen Germany
Department of Urology, Semmelweis University, Budapest, Hungary
Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
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