Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study
Non-schistosomiasis related-squamous cell carcinoma of urinary bladder (NSR-SCCUB) is a rare tumor subtype distinct from urothelial carcinoma (UC). Studies assessing molecular biomarkers in bladder cancer have generally focused on UC, and genomic data of NSR-SCCUB is limited. We aim to provide addit...
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| Veröffentlicht in: | PloS one 2021-12, Vol.16 (12), p.e0259272-e0259272 |
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| creator | Al-Ezzi, Esmail M Veitch, Zachary W Salah, Samer H Van der Kwast, Theodorus H Stockley, Tracy L Selvarajah, Shamini Zhang, Tong Sridhar, Srikala S Sacher, Adrian G Fallah-Rad, Nazanin Kulkarni, Girish S Zlotta, Alexandre R Finelli, Antonio Hansen, Aaron R |
| description | Non-schistosomiasis related-squamous cell carcinoma of urinary bladder (NSR-SCCUB) is a rare tumor subtype distinct from urothelial carcinoma (UC). Studies assessing molecular biomarkers in bladder cancer have generally focused on UC, and genomic data of NSR-SCCUB is limited. We aim to provide additional insight into the molecular underpinnings of this rare entity.
NSR-SCCUB patients were identified retrospectively at Princess Margaret Cancer Centre between 2002 and 2017. Demographics, disease characteristics, therapeutic approaches, and outcomes were collected. Tissue samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Kaplan-Meier method was used to estimate the disease-free survival and overall survival (OS).
Overall, 11 patients with NSR-SCCUB were identified between 2002 and 2017 with adequate tissue samples. Median age was 71 years (45-86), predominantly male (63.6%). At time of diagnosis, 9 patients (81.8%) had muscle-invasive disease, 1 (9.1%) had non-muscle invasive, and 1 (9.1%) had advanced disease. Nine (81.8%) patients had radical cystectomy and pelvic lymph nodes dissection. Eight (72.7%) patients had pT3 or pT4 with N0, and 5 (45.5%) were grade 3. Median OS was 12.5 months (95% CI 7.7-17.2 months). Single nucleotide variants or insertion/deletions were identified in TP53, TERT, PIK3CA, PTEN, CREBBP, FBXW7, and FGFR3. Amplifications were found in CCND1, and EGFR.
NSR-SCCUB has potentially actionable genomic alterations with anticancer agents and many of these aberrations are also seen in UC. The recruitment of NSR-SCCUB patients harboring such mutations should be considered in biomarker driven urinary bladder cancer studies. |
| doi_str_mv | 10.1371/journal.pone.0259272 |
| format | Article |
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NSR-SCCUB patients were identified retrospectively at Princess Margaret Cancer Centre between 2002 and 2017. Demographics, disease characteristics, therapeutic approaches, and outcomes were collected. Tissue samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Kaplan-Meier method was used to estimate the disease-free survival and overall survival (OS).
Overall, 11 patients with NSR-SCCUB were identified between 2002 and 2017 with adequate tissue samples. Median age was 71 years (45-86), predominantly male (63.6%). At time of diagnosis, 9 patients (81.8%) had muscle-invasive disease, 1 (9.1%) had non-muscle invasive, and 1 (9.1%) had advanced disease. Nine (81.8%) patients had radical cystectomy and pelvic lymph nodes dissection. Eight (72.7%) patients had pT3 or pT4 with N0, and 5 (45.5%) were grade 3. Median OS was 12.5 months (95% CI 7.7-17.2 months). Single nucleotide variants or insertion/deletions were identified in TP53, TERT, PIK3CA, PTEN, CREBBP, FBXW7, and FGFR3. Amplifications were found in CCND1, and EGFR.
NSR-SCCUB has potentially actionable genomic alterations with anticancer agents and many of these aberrations are also seen in UC. The recruitment of NSR-SCCUB patients harboring such mutations should be considered in biomarker driven urinary bladder cancer studies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0259272</identifier><identifier>PMID: 34851968</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Aged, 80 and over ; Anticancer properties ; Antitumor agents ; Biology and Life Sciences ; Biomarkers ; Biomarkers, Tumor - genetics ; Bladder ; Bladder cancer ; Cancer therapies ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - pathology ; Cdc4 protein ; Chemotherapy ; Class I Phosphatidylinositol 3-Kinases - genetics ; Conflicts of interest ; CREB-Binding Protein - genetics ; Cyclin D1 - genetics ; Data collection ; Demographics ; Demography ; ErbB Receptors - genetics ; F-Box-WD Repeat-Containing Protein 7 - genetics ; Female ; Fibroblast growth factor receptors ; Genetic aspects ; Genomics ; Health care networks ; Hematology ; Humans ; Invasiveness ; Lymph nodes ; Lymphatic system ; Male ; Medical laboratories ; Medicine and Health Sciences ; Middle Aged ; Muscles ; Mutation ; Nucleotides ; Oncology ; p53 Protein ; Pathology ; Physiological aspects ; PTEN Phosphohydrolase - genetics ; PTEN protein ; Radiation therapy ; Receptor, Fibroblast Growth Factor, Type 3 - genetics ; Schistosomiasis ; Squamous cell carcinoma ; Survival ; Telomerase - genetics ; Tumor Suppressor Protein p53 - genetics ; Tumors ; Urinary bladder ; Urinary Bladder Neoplasms - genetics ; Urinary Bladder Neoplasms - pathology ; Urothelial carcinoma</subject><ispartof>PloS one, 2021-12, Vol.16 (12), p.e0259272-e0259272</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Al-ezzi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Al-ezzi et al 2021 Al-ezzi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c622t-78a2742d3a7e94c568202dd1007954e4de17d69222a1eb8aa4a068ac789897973</citedby><cites>FETCH-LOGICAL-c622t-78a2742d3a7e94c568202dd1007954e4de17d69222a1eb8aa4a068ac789897973</cites><orcidid>0000-0002-2363-8707</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635362/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635362/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34851968$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gao, Xin</contributor><creatorcontrib>Al-Ezzi, Esmail M</creatorcontrib><creatorcontrib>Veitch, Zachary W</creatorcontrib><creatorcontrib>Salah, Samer H</creatorcontrib><creatorcontrib>Van der Kwast, Theodorus H</creatorcontrib><creatorcontrib>Stockley, Tracy L</creatorcontrib><creatorcontrib>Selvarajah, Shamini</creatorcontrib><creatorcontrib>Zhang, Tong</creatorcontrib><creatorcontrib>Sridhar, Srikala S</creatorcontrib><creatorcontrib>Sacher, Adrian G</creatorcontrib><creatorcontrib>Fallah-Rad, Nazanin</creatorcontrib><creatorcontrib>Kulkarni, Girish S</creatorcontrib><creatorcontrib>Zlotta, Alexandre R</creatorcontrib><creatorcontrib>Finelli, Antonio</creatorcontrib><creatorcontrib>Hansen, Aaron R</creatorcontrib><title>Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Non-schistosomiasis related-squamous cell carcinoma of urinary bladder (NSR-SCCUB) is a rare tumor subtype distinct from urothelial carcinoma (UC). Studies assessing molecular biomarkers in bladder cancer have generally focused on UC, and genomic data of NSR-SCCUB is limited. We aim to provide additional insight into the molecular underpinnings of this rare entity.
NSR-SCCUB patients were identified retrospectively at Princess Margaret Cancer Centre between 2002 and 2017. Demographics, disease characteristics, therapeutic approaches, and outcomes were collected. Tissue samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Kaplan-Meier method was used to estimate the disease-free survival and overall survival (OS).
Overall, 11 patients with NSR-SCCUB were identified between 2002 and 2017 with adequate tissue samples. Median age was 71 years (45-86), predominantly male (63.6%). At time of diagnosis, 9 patients (81.8%) had muscle-invasive disease, 1 (9.1%) had non-muscle invasive, and 1 (9.1%) had advanced disease. Nine (81.8%) patients had radical cystectomy and pelvic lymph nodes dissection. Eight (72.7%) patients had pT3 or pT4 with N0, and 5 (45.5%) were grade 3. Median OS was 12.5 months (95% CI 7.7-17.2 months). Single nucleotide variants or insertion/deletions were identified in TP53, TERT, PIK3CA, PTEN, CREBBP, FBXW7, and FGFR3. Amplifications were found in CCND1, and EGFR.
NSR-SCCUB has potentially actionable genomic alterations with anticancer agents and many of these aberrations are also seen in UC. The recruitment of NSR-SCCUB patients harboring such mutations should be considered in biomarker driven urinary bladder cancer studies.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anticancer properties</subject><subject>Antitumor agents</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Bladder</subject><subject>Bladder cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cdc4 protein</subject><subject>Chemotherapy</subject><subject>Class I Phosphatidylinositol 3-Kinases - genetics</subject><subject>Conflicts of interest</subject><subject>CREB-Binding Protein - genetics</subject><subject>Cyclin D1 - genetics</subject><subject>Data collection</subject><subject>Demographics</subject><subject>Demography</subject><subject>ErbB Receptors - genetics</subject><subject>F-Box-WD Repeat-Containing Protein 7 - genetics</subject><subject>Female</subject><subject>Fibroblast growth factor receptors</subject><subject>Genetic aspects</subject><subject>Genomics</subject><subject>Health care networks</subject><subject>Hematology</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Lymph nodes</subject><subject>Lymphatic system</subject><subject>Male</subject><subject>Medical laboratories</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Muscles</subject><subject>Mutation</subject><subject>Nucleotides</subject><subject>Oncology</subject><subject>p53 Protein</subject><subject>Pathology</subject><subject>Physiological aspects</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN protein</subject><subject>Radiation therapy</subject><subject>Receptor, Fibroblast Growth Factor, Type 3 - genetics</subject><subject>Schistosomiasis</subject><subject>Squamous cell carcinoma</subject><subject>Survival</subject><subject>Telomerase - genetics</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumors</subject><subject>Urinary bladder</subject><subject>Urinary Bladder Neoplasms - genetics</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Urothelial carcinoma</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99u0zAUxiMEYmPwBggiISG4aHHs2LG5QKomGJUmTeLfrXVqn7au0riznWnjDXhrnLWbWrQLlItEzu_7Ts6Xc4riZUXGFWuqDyvfhw7a8cZ3OCaUK9rQR8VxpRgdCUrY473no-JZjCtCOJNCPC2OWC15pYQ8Lv6cYefXzpRmCQFMwuB-Q3K-K_287Hw3imbpYvIxQxBdHAVsIaEt42UPa9_H0mDblgaCcdkIBllaYtkH10G4KWctWIvhYzkpA6bg4wZNcldY4vWm9QGSz1BMvb15XjyZQxvxxe5-Uvz88vnH6dfR-cXZ9HRyPjKC0jRqJNCmppZBg6o2XEhKqLUVIY3iNdYWq8YKRSmFCmcSoAYiJJhGKqka1bCT4vXWN9ePepdi1FQQXsma1QMx3RLWw0pvglvnTrQHp28PfFhoCMmZFjWyRim0jKGZ17SpgJuZJBypIdnQQvb6tKvWz9ZoDXYpQHtgevimc0u98FdaCsaZoNng3c4g-MseY9JrF4fMocMc_-13c6UIVxl98w_6cHc7agG5AdfNfa5rBlM9EbKuORd08Bo_QOXLYp6WPHJzl88PBO8PBJlJeJ0W0Meop9-__T978euQfbvHLhHatIy-7YcZjYdgvQVNnrIYcH4fckX0sDF3aehhY_RuY7Ls1f4PuhfdrQj7C67UE4E</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Al-Ezzi, Esmail M</creator><creator>Veitch, Zachary W</creator><creator>Salah, Samer H</creator><creator>Van der Kwast, Theodorus H</creator><creator>Stockley, Tracy L</creator><creator>Selvarajah, Shamini</creator><creator>Zhang, Tong</creator><creator>Sridhar, Srikala S</creator><creator>Sacher, Adrian G</creator><creator>Fallah-Rad, Nazanin</creator><creator>Kulkarni, Girish S</creator><creator>Zlotta, Alexandre R</creator><creator>Finelli, Antonio</creator><creator>Hansen, Aaron R</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-2363-8707</orcidid></search><sort><creationdate>20211201</creationdate><title>Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study</title><author>Al-Ezzi, Esmail M ; Veitch, Zachary W ; Salah, Samer H ; Van der Kwast, Theodorus H ; Stockley, Tracy L ; Selvarajah, Shamini ; Zhang, Tong ; Sridhar, Srikala S ; Sacher, Adrian G ; Fallah-Rad, Nazanin ; Kulkarni, Girish S ; Zlotta, Alexandre R ; Finelli, Antonio ; Hansen, Aaron R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c622t-78a2742d3a7e94c568202dd1007954e4de17d69222a1eb8aa4a068ac789897973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Anticancer properties</topic><topic>Antitumor agents</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - 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genetics</topic><topic>PTEN protein</topic><topic>Radiation therapy</topic><topic>Receptor, Fibroblast Growth Factor, Type 3 - genetics</topic><topic>Schistosomiasis</topic><topic>Squamous cell carcinoma</topic><topic>Survival</topic><topic>Telomerase - genetics</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumors</topic><topic>Urinary bladder</topic><topic>Urinary Bladder Neoplasms - genetics</topic><topic>Urinary Bladder Neoplasms - pathology</topic><topic>Urothelial carcinoma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Al-Ezzi, Esmail M</creatorcontrib><creatorcontrib>Veitch, Zachary W</creatorcontrib><creatorcontrib>Salah, Samer H</creatorcontrib><creatorcontrib>Van der Kwast, Theodorus H</creatorcontrib><creatorcontrib>Stockley, Tracy L</creatorcontrib><creatorcontrib>Selvarajah, Shamini</creatorcontrib><creatorcontrib>Zhang, Tong</creatorcontrib><creatorcontrib>Sridhar, Srikala S</creatorcontrib><creatorcontrib>Sacher, Adrian G</creatorcontrib><creatorcontrib>Fallah-Rad, Nazanin</creatorcontrib><creatorcontrib>Kulkarni, Girish S</creatorcontrib><creatorcontrib>Zlotta, Alexandre R</creatorcontrib><creatorcontrib>Finelli, Antonio</creatorcontrib><creatorcontrib>Hansen, Aaron R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Al-Ezzi, Esmail M</au><au>Veitch, Zachary W</au><au>Salah, Samer H</au><au>Van der Kwast, Theodorus H</au><au>Stockley, Tracy L</au><au>Selvarajah, Shamini</au><au>Zhang, Tong</au><au>Sridhar, Srikala S</au><au>Sacher, Adrian G</au><au>Fallah-Rad, Nazanin</au><au>Kulkarni, Girish S</au><au>Zlotta, Alexandre R</au><au>Finelli, Antonio</au><au>Hansen, Aaron R</au><au>Gao, Xin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>16</volume><issue>12</issue><spage>e0259272</spage><epage>e0259272</epage><pages>e0259272-e0259272</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Non-schistosomiasis related-squamous cell carcinoma of urinary bladder (NSR-SCCUB) is a rare tumor subtype distinct from urothelial carcinoma (UC). Studies assessing molecular biomarkers in bladder cancer have generally focused on UC, and genomic data of NSR-SCCUB is limited. We aim to provide additional insight into the molecular underpinnings of this rare entity.
NSR-SCCUB patients were identified retrospectively at Princess Margaret Cancer Centre between 2002 and 2017. Demographics, disease characteristics, therapeutic approaches, and outcomes were collected. Tissue samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Kaplan-Meier method was used to estimate the disease-free survival and overall survival (OS).
Overall, 11 patients with NSR-SCCUB were identified between 2002 and 2017 with adequate tissue samples. Median age was 71 years (45-86), predominantly male (63.6%). At time of diagnosis, 9 patients (81.8%) had muscle-invasive disease, 1 (9.1%) had non-muscle invasive, and 1 (9.1%) had advanced disease. Nine (81.8%) patients had radical cystectomy and pelvic lymph nodes dissection. Eight (72.7%) patients had pT3 or pT4 with N0, and 5 (45.5%) were grade 3. Median OS was 12.5 months (95% CI 7.7-17.2 months). Single nucleotide variants or insertion/deletions were identified in TP53, TERT, PIK3CA, PTEN, CREBBP, FBXW7, and FGFR3. Amplifications were found in CCND1, and EGFR.
NSR-SCCUB has potentially actionable genomic alterations with anticancer agents and many of these aberrations are also seen in UC. The recruitment of NSR-SCCUB patients harboring such mutations should be considered in biomarker driven urinary bladder cancer studies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34851968</pmid><doi>10.1371/journal.pone.0259272</doi><tpages>e0259272</tpages><orcidid>https://orcid.org/0000-0002-2363-8707</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2021-12, Vol.16 (12), p.e0259272-e0259272 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2605184347 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aged Aged, 80 and over Anticancer properties Antitumor agents Biology and Life Sciences Biomarkers Biomarkers, Tumor - genetics Bladder Bladder cancer Cancer therapies Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Cdc4 protein Chemotherapy Class I Phosphatidylinositol 3-Kinases - genetics Conflicts of interest CREB-Binding Protein - genetics Cyclin D1 - genetics Data collection Demographics Demography ErbB Receptors - genetics F-Box-WD Repeat-Containing Protein 7 - genetics Female Fibroblast growth factor receptors Genetic aspects Genomics Health care networks Hematology Humans Invasiveness Lymph nodes Lymphatic system Male Medical laboratories Medicine and Health Sciences Middle Aged Muscles Mutation Nucleotides Oncology p53 Protein Pathology Physiological aspects PTEN Phosphohydrolase - genetics PTEN protein Radiation therapy Receptor, Fibroblast Growth Factor, Type 3 - genetics Schistosomiasis Squamous cell carcinoma Survival Telomerase - genetics Tumor Suppressor Protein p53 - genetics Tumors Urinary bladder Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - pathology Urothelial carcinoma |
| title | Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study |
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