{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["van den Boogaard ML"],"funding":["ZonMW Vidi grant","European Research Council","Villa Joep Foundation","ZonMw","Stichting Kinderen Kankervrij","Oncode Institute","Dutch Cancer Society (KWF)/Alpe d&apos;HuZes Bas Mulder Award"],"pagination":["e2007898118"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8433536"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["118(36)"],"pubmed_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 <i>OGG1</i> or <i>MUTYH</i> 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 <i>OGG1</i> or <i>MUTYH</i> show increased 8-oxoG levels compared to wild-type cells. We used CRISPR-Cas9 genome editing to create knockout clones of <i>MUTYH</i> and <i>OGG"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Defects in 8-oxo-guanine repair pathway cause high frequency of C > A substitutions in neuroblastoma."],"pmcid":["PMC8433536"],"funding_grant_id":["91716482","N/A","10218"],"pubmed_authors":["van Gerven MR","van Boxtel R","Zwijnenburg DA","Essing AHW","Koster J","Hakkert A","Schild L","Drost J","van den Boogaard ML","Ebus ME","Hoyng LL","Dolman MEM","Koopmans B","Molenaar JJ","Helleday T","Versteeg R","Oka R","Molenaar P"],"additional_accession":[]},"is_claimable":false,"name":"Defects in 8-oxo-guanine repair pathway cause high frequency of C > A substitutions in neuroblastoma.","description":"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 <i>OGG1</i> or <i>MUTYH</i> 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 <i>OGG1</i> or <i>MUTYH</i> show increased 8-oxoG levels compared to wild-type cells. We used CRISPR-Cas9 genome editing to create knockout clones of <i>MUTYH</i> and <i>OGG","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2026-05-08T16:39:21.976Z","creation":"2025-06-01T00:57:18.491Z"},"accession":"S-EPMC8433536","cross_references":{"pubmed":["34479993"],"doi":["10.1073/pnas.2007898118"]}}