{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T14:45:00Z","timestamp":1784299500195,"version":"3.55.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The survival of glioblastoma patients is poor. Median survival after diagnosis is 15 months, despite treatment involving surgical resection, radiotherapy, and\/or temozolomide chemotherapy. Identification of novel targets and stratification strategies of glioblastoma patients to improve patient survival is urgently needed. Whole-genome sequencing (WGS) is the most comprehensive means to identify such DNA-level targets. We report a unique set of WGS samples along with comprehensive analyses of the glioblastoma genome and potential clinical impact of WGS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Our cohort consisted of 42 glioblastoma tumor tissue and matched whole-blood samples, which were whole-genome sequenced as part of the CPCT-02 study. Somatic single-nucleotide variants, small insertions\/deletions, multi-nucleotide variants, copy-number alterations (CNAs), and structural variants were analyzed. These aberrations were harnessed to investigate driver genes, enrichments in CNAs, mutational signatures, fusion genes, and potential targeted therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tumor mutational burden (TMB) was similar to other WGS efforts (1\u2013342 mutations per megabase pair). Mutational analysis in low TMB samples showed that the age-related CpG demethylation signature was dominant, while hyper- and ultramutated tumors had additional defective DNA mismatch repair signatures and showed microsatellite instability in their genomes. We detected chromothripsis in 24% of our cohort, recurrently on chromosomes 1 and 12. Recurrent noncoding regions only resulted in TERT promoter variants. Finally, we found biomarkers and potentially druggable changes in all but one of our tumor samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>With high-quality WGS data and comprehensive methods, we identified the landscape of driver gene events and druggable targets in glioblastoma patients.<\/jats:p><\/jats:sec>","DOI":"10.1093\/noajnl\/vdab177","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T14:56:19Z","timestamp":1638370579000},"source":"Crossref","is-referenced-by-count":5,"title":["Landscape of driver gene events, biomarkers, and druggable targets identified by whole-genome sequencing of glioblastomas"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9738-9988","authenticated-orcid":false,"given":"Wesley S","family":"van de Geer","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The 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