{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:56:36Z","timestamp":1790628996144,"version":"4.1.0"},"reference-count":32,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"\n Purpose<\/jats:title>\n Next-generation sequencing\u2013based mutational signatures are frequently used to identify tumors with specific DNA repair deficiencies for targeted therapeutic strategies. Although mutational signatures are commonly derived from whole-exome or whole-genome sequencing data, patients often undergo tumor sequencing using more limited targeted panels that typically encompass several hundred cancer-associated genes. Identifying clinically relevant mutational signatures from targeted panel data requires new approaches capable of deriving signatures from the more limited sequencing data.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Using publicly available panel sequencing data, we derived and validated a panel sequencing\u2013based composite mutational signature associated with nucleotide excision repair (NER) deficiency induced by inactivating\n ERCC2<\/jats:italic>\n mutations in bladder cancer.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We found that\n ERCC2<\/jats:italic>\n wild-type (WT) bladder cancer cases that have high levels of this mutational signature respond better to neoadjuvant platinum therapy and have improved overall survival compared with\n ERCC2<\/jats:italic>\n WT cases with low levels of the signature. We also found that other solid tumor types with\n ERCC2<\/jats:italic>\n mutations also show the characteristic mutational signature seen in NER-deficient\n ERCC2<\/jats:italic>\n -mutant bladder cancers, suggesting a novel approach to therapeutically target these\n ERCC2<\/jats:italic>\n -mutant solid tumors beyond bladder cancer.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Mutational signature\u2013based NER deficiency status can be determined in panel sequencing data of tumor biopsies. This could be used to investigate the connection between NER deficiency and response to neoadjuvant platinum-based chemotherapy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/po-26-00329","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:59:12Z","timestamp":1790625552000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Identification of an\n ERCC2<\/i>\n Mutation\u2013Associated Mutational Signature of Nucleotide Excision Repair Deficiency in Targeted Panel Sequencing Data"],"prefix":"10.1200","volume":"10","author":[{"given":"Olivera","family":"Stojkova","sequence":"first","affiliation":[{"name":"Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3290-3971","authenticated-orcid":true,"given":"Judit","family":"B\u00f6rcs\u00f6k","sequence":"additional","affiliation":[{"name":"Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark"},{"name":"Translational Cancer Genomics Group, Danish Cancer Institute, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsofia","family":"Sztupinszki","sequence":"additional","affiliation":[{"name":"Translational Cancer Genomics Group, Danish Cancer Institute, Copenhagen, Denmark"},{"name":"Computational Health Informatics Program, Boston Children's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0308-6615","authenticated-orcid":true,"given":"Miklos","family":"Diossy","sequence":"additional","affiliation":[{"name":"Computational Health Informatics Program, Boston Children's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8494-6340","authenticated-orcid":true,"given":"Aurel","family":"Prosz","sequence":"additional","affiliation":[{"name":"Translational Cancer Genomics Group, Danish Cancer Institute, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3351-787X","authenticated-orcid":true,"given":"Alexander","family":"Neil","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7939-7343","authenticated-orcid":true,"given":"Kent W.","family":"Mouw","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus S.","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5395-7509","authenticated-orcid":true,"given":"Zoltan","family":"Szallasi","sequence":"additional","affiliation":[{"name":"Translational Cancer Genomics Group, Danish Cancer Institute, Copenhagen, Denmark"},{"name":"Computational Health Informatics Program, Boston Children's Hospital, Boston, MA"},{"name":"Department of Bioinformatics, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam7344"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1001"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-0623"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3316"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-1943-3"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0390-2"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-0673"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3322"},{"key":"e_1_3_8_10_2","unstructured":"GDC: https:\/\/portal.gdc.cancer.gov"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.1056"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.07.009"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18640-0"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0151"},{"key":"e_1_3_8_15_2","volume-title":"Synapse\u2014Project GENIE Data Portal","unstructured":"Synapse\u2014Project GENIE Data Portal. https:\/\/synapse.org\/genie"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI186688"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-022-08357-3"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.230219.117"},{"key":"e_1_3_8_20_2","doi-asserted-by":"publisher","DOI":"10.32614\/RJ-2021-041"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v028.i05"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v098.i11"},{"key":"e_1_3_8_23_2","unstructured":"GITHUB: https:\/\/github.com\/jud-b\/ERCC2mut"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-120213-092015"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-052621-091205"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3557"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-0981"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17676"},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911361"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611310"},{"key":"e_1_3_8_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr1501341"},{"key":"e_1_3_8_32_2","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2020-000744"},{"key":"e_1_3_8_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2025.02.005"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-26-00329","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:59:14Z","timestamp":1790625554000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-26-00329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1200\/PO-26-00329"],"URL":"https:\/\/doi.org\/10.1200\/po-26-00329","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-10","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2600329"}}