Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor
Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon sig...
Ausführliche Beschreibung
Autor*in: |
Bou Zerdan, Maroun [verfasserIn] |
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E-Artikel |
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Englisch |
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2023 |
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© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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Übergeordnetes Werk: |
Enthalten in: Molecular diagnosis & therapy - [S.l.] : Springer International, 2006, 27(2023), 4 vom: 17. Mai, Seite 475-485 |
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Übergeordnetes Werk: |
volume:27 ; year:2023 ; number:4 ; day:17 ; month:05 ; pages:475-485 |
Links: |
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DOI / URN: |
10.1007/s40291-023-00647-0 |
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Katalog-ID: |
SPR052075710 |
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520 | |a Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. Methods There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC. Conclusions An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment. | ||
700 | 1 | |a Bratslavsky, Gennady |4 aut | |
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700 | 1 | |a Ross, Jeffrey |4 aut | |
700 | 1 | |a Huang, Richard |4 aut | |
700 | 1 | |a Basnet, Alina |4 aut | |
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10.1007/s40291-023-00647-0 doi (DE-627)SPR052075710 (SPR)s40291-023-00647-0-e DE-627 ger DE-627 rakwb eng Bou Zerdan, Maroun verfasserin (orcid)0000-0002-9229-3079 aut Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. Methods There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC. Conclusions An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment. Bratslavsky, Gennady aut Jacob, Joseph aut Ross, Jeffrey aut Huang, Richard aut Basnet, Alina aut Enthalten in Molecular diagnosis & therapy [S.l.] : Springer International, 2006 27(2023), 4 vom: 17. Mai, Seite 475-485 (DE-627)51122799X (DE-600)2232973-0 1179-2000 nnns volume:27 year:2023 number:4 day:17 month:05 pages:475-485 https://dx.doi.org/10.1007/s40291-023-00647-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 27 2023 4 17 05 475-485 |
spelling |
10.1007/s40291-023-00647-0 doi (DE-627)SPR052075710 (SPR)s40291-023-00647-0-e DE-627 ger DE-627 rakwb eng Bou Zerdan, Maroun verfasserin (orcid)0000-0002-9229-3079 aut Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. Methods There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC. Conclusions An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment. Bratslavsky, Gennady aut Jacob, Joseph aut Ross, Jeffrey aut Huang, Richard aut Basnet, Alina aut Enthalten in Molecular diagnosis & therapy [S.l.] : Springer International, 2006 27(2023), 4 vom: 17. Mai, Seite 475-485 (DE-627)51122799X (DE-600)2232973-0 1179-2000 nnns volume:27 year:2023 number:4 day:17 month:05 pages:475-485 https://dx.doi.org/10.1007/s40291-023-00647-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 27 2023 4 17 05 475-485 |
allfields_unstemmed |
10.1007/s40291-023-00647-0 doi (DE-627)SPR052075710 (SPR)s40291-023-00647-0-e DE-627 ger DE-627 rakwb eng Bou Zerdan, Maroun verfasserin (orcid)0000-0002-9229-3079 aut Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. Methods There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC. Conclusions An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment. Bratslavsky, Gennady aut Jacob, Joseph aut Ross, Jeffrey aut Huang, Richard aut Basnet, Alina aut Enthalten in Molecular diagnosis & therapy [S.l.] : Springer International, 2006 27(2023), 4 vom: 17. Mai, Seite 475-485 (DE-627)51122799X (DE-600)2232973-0 1179-2000 nnns volume:27 year:2023 number:4 day:17 month:05 pages:475-485 https://dx.doi.org/10.1007/s40291-023-00647-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 27 2023 4 17 05 475-485 |
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10.1007/s40291-023-00647-0 doi (DE-627)SPR052075710 (SPR)s40291-023-00647-0-e DE-627 ger DE-627 rakwb eng Bou Zerdan, Maroun verfasserin (orcid)0000-0002-9229-3079 aut Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. Methods There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC. Conclusions An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment. Bratslavsky, Gennady aut Jacob, Joseph aut Ross, Jeffrey aut Huang, Richard aut Basnet, Alina aut Enthalten in Molecular diagnosis & therapy [S.l.] : Springer International, 2006 27(2023), 4 vom: 17. Mai, Seite 475-485 (DE-627)51122799X (DE-600)2232973-0 1179-2000 nnns volume:27 year:2023 number:4 day:17 month:05 pages:475-485 https://dx.doi.org/10.1007/s40291-023-00647-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 27 2023 4 17 05 475-485 |
allfieldsSound |
10.1007/s40291-023-00647-0 doi (DE-627)SPR052075710 (SPR)s40291-023-00647-0-e DE-627 ger DE-627 rakwb eng Bou Zerdan, Maroun verfasserin (orcid)0000-0002-9229-3079 aut Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. Methods There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC. Conclusions An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment. Bratslavsky, Gennady aut Jacob, Joseph aut Ross, Jeffrey aut Huang, Richard aut Basnet, Alina aut Enthalten in Molecular diagnosis & therapy [S.l.] : Springer International, 2006 27(2023), 4 vom: 17. Mai, Seite 475-485 (DE-627)51122799X (DE-600)2232973-0 1179-2000 nnns volume:27 year:2023 number:4 day:17 month:05 pages:475-485 https://dx.doi.org/10.1007/s40291-023-00647-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 27 2023 4 17 05 475-485 |
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Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. 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Bou Zerdan, Maroun |
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Bou Zerdan, Maroun Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor |
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Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor |
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Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor |
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Bou Zerdan, Maroun Bratslavsky, Gennady Jacob, Joseph Ross, Jeffrey Huang, Richard Basnet, Alina |
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urothelial bladder cancer: genomic alterations in fibroblast growth factor receptor |
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Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor |
abstract |
Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. Methods There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC. Conclusions An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
abstractGer |
Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. Methods There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC. Conclusions An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
abstract_unstemmed |
Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. Methods There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC. Conclusions An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor |
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https://dx.doi.org/10.1007/s40291-023-00647-0 |
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Bratslavsky, Gennady Jacob, Joseph Ross, Jeffrey Huang, Richard Basnet, Alina |
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Bratslavsky, Gennady Jacob, Joseph Ross, Jeffrey Huang, Richard Basnet, Alina |
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Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background and Objective Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. Methods There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3). Results The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. 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score |
7.3998976 |