{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T18:41:24Z","timestamp":1772822484209,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974398"],"award-info":[{"award-number":["81974398"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103097"],"award-info":[{"award-number":["82103097"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172785"],"award-info":[{"award-number":["82172785"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The mutational pattern of homologous recombination repair (HRR)\u2010associated gene alterations in Chinese urothelial carcinoma (UC) necessitates comprehensive sequencing efforts, and the clinical implications of HRR gene mutations in UC remain to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We delineated the mutational landscape of 343 Chinese UC patients from West China Hospital and 822 patients from The Cancer Genome Atlas (TCGA) using next\u2010generation sequencing (NGS). Data from 182 metastatic UC patients from MSK\u2010IMPACT cohort were used to assess the association between HRR mutations and immunotherapy efficacy. Comprehensive transcriptomic analysis was performed to explore the impact of HRR mutations on tumor immune microenvironment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among Chinese UC patients, 34% harbored HRR gene mutations, with <jats:italic>BRCA2<\/jats:italic>, <jats:italic>ATM<\/jats:italic>, <jats:italic>BRCA1<\/jats:italic>, <jats:italic>CDK12<\/jats:italic>, and <jats:italic>RAD51C<\/jats:italic> being the most prevalently mutated genes. Mutational signatures contributing to UC differed between patients with and without HRR mutations. Signature 22 for exposure to aristolochic acid was only observed in Chinese UC patients. The presence of HRR mutations was correlated with higher tumor mutational burden, neoantigen burden, and PD\u2010L1 expression. Importantly, patients with HRR mutations exhibited significantly improved prognosis following immunotherapy compared to those without HRR mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings provide valuable insights into the genomic landscape of Chinese UC patients and underscore the molecular rationale for utilizing immunotherapy in UC patients with HRR mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6725","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T18:49:14Z","timestamp":1700678954000},"page":"22370-22380","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The mutational pattern of homologous recombination repair genes in urothelial carcinoma and its correlation with immunotherapeutic response"],"prefix":"10.1002","volume":"12","author":[{"given":"Junru","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfeng","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9010-3748","authenticated-orcid":false,"given":"Huanhuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Acornmed Biotechnology Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangxi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zilin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanrui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Acornmed Biotechnology Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Lou","sequence":"additional","affiliation":[{"name":"Acornmed Biotechnology Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanbo","family":"Cao","sequence":"additional","affiliation":[{"name":"Acornmed Biotechnology Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4721-0016","authenticated-orcid":false,"given":"Jiayue","family":"Qin","sequence":"additional","affiliation":[{"name":"Acornmed Biotechnology Co., Ltd.  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2895-1361","authenticated-orcid":false,"given":"Huina","family":"Wang","sequence":"additional","affiliation":[{"name":"Acornmed Biotechnology Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banghua","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0818-8151","authenticated-orcid":false,"given":"Hao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2013.02.002"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1992.10.7.1066"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2021.09.026"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2022.0041"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx692"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613683"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01213"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32455-2"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00152-2"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30541-6"},{"key":"e_1_2_12_13_1","first-page":"PO.17.00286","article-title":"Prevalence of homologous recombination\u2010related gene mutations across multiple cancer types","volume":"2018","author":"Heeke AL","year":"2018","journal-title":"JCO Precis Oncol"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2015.21"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19406-4"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01059-5"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.02.011"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0195"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32729"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13839"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2514"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14601-9"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar7939"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005965"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts146"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.7642"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-2101-2"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3147"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12477"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15290"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568009620999200918121456"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6175"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.09.006"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0312-8"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01579-0"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.023"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-0844-0"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2020.04.695"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.275453.115"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201846821"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007779"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.43251"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13101745"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.7740"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3529"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.871756"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0274-8"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00405"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00205"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1348"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801946"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.20892\/j.issn.2095-3941.2020.0089"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0787-5"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001406"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.053"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.6725","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T08:55:29Z","timestamp":1705222529000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.6725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,20]]},"references-count":54,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/cam4.6725"],"URL":"https:\/\/doi.org\/10.1002\/cam4.6725","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,20]]},"assertion":[{"value":"2023-08-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}