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It is likely that this is the tip of the iceberg and many children are underdiagnosed, as most of the analysis focuses on single or short nucleotide variants, not considering the full spectrum of DNA alterations. Hence, we applied optical genome mapping (OGM) to our cohort of 34 pediatric cancer patients to perform an unbiased germline screening and analyze the frequency of structural variants (SVs) and their impact on cancer predisposition. All children were clinically highly suspicious for germline alterations (concomitant conditions or congenital anomalies, positive family cancer history, particular cancer type, synchronous or metachronous tumors), but whole exome sequencing (WES) had failed to detect pathogenic variants in cancer predisposing genes. OGM detected a median of 49 rare SVs (range 27\u2010149) per patient. By analysis of 18 patient\u2010parent trios, we identified three de novo SVs. Moreover, we discovered a likely pathogenic deletion of exon 3 in the known cancer predisposition gene <jats:italic>BRCA2<\/jats:italic>, and identified a duplication in <jats:italic>RPA1<\/jats:italic>, which might represent a new cancer predisposition gene. We conclude that optical genome mapping is a suitable tool for detecting potentially predisposing SVs in addition to WES in pediatric cancer patients.<\/jats:p>","DOI":"10.1002\/ijc.34721","type":"journal-article","created":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T13:04:48Z","timestamp":1696079088000},"page":"607-614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Optical genome mapping identifies structural variants in potentially new cancer predisposition candidate genes in pediatric cancer patients"],"prefix":"10.1002","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5394-0907","authenticated-orcid":false,"given":"Rabea","family":"Wagener","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"},{"name":"German Cancer Consortium (DKTK), partner 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