{"entity": "researcher", "timestamp": "2026-08-20T21:23:34.442Z", "family": "van Gerven", "given": "Michael R", "initials": "MR", "orcid": "0000-0001-5241-8810", "affiliations": ["Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/f062c944ea324ae699d0225b365a790b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/f062c944ea324ae699d0225b365a790b"}}, "publications": [{"entity": "publication", "iuid": "e37a961ddf5c4d83b2ab298494d17052", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e37a961ddf5c4d83b2ab298494d17052.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e37a961ddf5c4d83b2ab298494d17052"}}, "title": "Defects in 8-oxo-guanine repair pathway cause high frequency of C > A substitutions in neuroblastoma.", "authors": [{"family": "van den Boogaard", "given": "Marlinde L", "initials": "ML", "orcid": "0000-0002-3713-5270", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3042f6038437434b88360c13945bbe59.json"}}, {"family": "Oka", "given": "Rurika", "initials": "R", "orcid": "0000-0003-4107-7250", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/778b1be91d2244189ca425a5895735a2.json"}}, {"family": "Hakkert", "given": "Anne", "initials": "A"}, {"family": "Schild", "given": "Linda", "initials": "L"}, {"family": "Ebus", "given": "Marli E", "initials": "ME", "orcid": "0000-0002-8181-8941", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b81e10b8a23649cfafae6ca45e7f3014.json"}}, {"family": "van Gerven", "given": "Michael R", "initials": "MR", "orcid": "0000-0001-5241-8810", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f062c944ea324ae699d0225b365a790b.json"}}, {"family": "Zwijnenburg", "given": "Danny A", "initials": "DA"}, {"family": "Molenaar", "given": "Piet", "initials": "P"}, {"family": "Hoyng", "given": "Lieke L", "initials": "LL"}, {"family": "Dolman", "given": "M Emmy M", "initials": "MEM"}, {"family": "Essing", "given": "Anke H W", "initials": "AHW"}, {"family": "Koopmans", "given": "Bianca", "initials": "B"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Drost", "given": "Jarno", "initials": "J", "orcid": "0000-0002-2941-6179", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b01477f3bad04636b42ddd5b5ace6cb1.json"}}, {"family": "van Boxtel", "given": "Ruben", "initials": "R", "orcid": "0000-0003-1285-2836", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2d492d3f71bc4586bd0398ef99f03a5b.json"}}, {"family": "Versteeg", "given": "Rogier", "initials": "R", "orcid": "0000-0001-7172-0388", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ecd554eb81c41d29c3667af93a761d5.json"}}, {"family": "Koster", "given": "Jan", "initials": "J", "orcid": "0000-0002-0890-7585", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cbc4487331414b64ab7e95a823e09cbb.json"}}, {"family": "Molenaar", "given": "Jan J", "initials": "JJ", "orcid": "0000-0002-2007-0431", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0636796fc05c4b0f9ce5df0ce0f8ff6e.json"}}], "type": "journal article", "published": "2021-09-07", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "118", "issue": "36", "issn-l": "0027-8424"}, "abstract": "Neuroblastomas are childhood tumors with frequent fatal relapses after induction treatment, which is related to tumor evolution with additional genomic events. Our whole-genome sequencing data analysis revealed a high frequency of somatic cytosine > adenine (C > A) substitutions in primary neuroblastoma tumors, which was associated with poor survival. We showed that increased levels of C > A substitutions correlate with copy number loss (CNL) of OGG1 or MUTYH Both genes encode DNA glycosylases that recognize 8-oxo-guanine (8-oxoG) lesions as a first step of 8-oxoG repair. Tumor organoid models with CNL of OGG1 or MUTYH show increased 8-oxoG levels compared to wild-type cells. We used CRISPR-Cas9 genome editing to create knockout clones of MUTYH and OGG1 in neuroblastoma cells. Whole-genome sequencing of single-cell OGG1 and MUTYH knockout clones identified an increased accumulation of C > A substitutions. Mutational signature analysis of these OGG1 and MUTYH knockout clones revealed enrichment for C > A signatures 18 and 36, respectively. Clustering analysis showed that the knockout clones group together with tumors containing OGG1 or MUTYH CNL. In conclusion, we demonstrate that defects in 8-oxoG repair cause accumulation of C > A substitutions in neuroblastoma, which contributes to mutagenesis and tumor evolution.", "doi": "10.1073/pnas.2007898118", "pmid": "34479993", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8433536"}, {"db": "pii", "key": "2007898118"}], "notes": [], "created": "2026-08-20T09:30:46.001Z", "modified": "2026-08-20T09:30:46.407Z"}]}