biostudies-literatureWei SJAlex's Lemonade Stand Foundation for Childhood CancerU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHSCancer Prevention and Research Institute of Texas368https://www.ebi.ac.uk/biostudies/studies/S-EPMC7224192biostudies-literatureUnknown11(5)Despite the improvement in clinical outcome with 13-cis-retinoic acid (13-cisRA) + anti-GD2 antibody + cytokine immunotherapy given in first response ~40% of high-risk neuroblastoma patients die of recurrent disease. MYCN genomic amplification is a biomarker of aggressive tumors in the childhood cancer neuroblastoma. MYCN expression is downregulated by 13-cisRA, a differentiating agent that is a component of neuroblastoma therapy. Although MYC amplification is rare in neuroblastoma at diagnosis, we report transcriptional activation of MYC medicated by the transcription factor OCT4, functionally replacing MYCN in 13-cisRA-resistant progressive disease neuroblastoma in large panels of patient-derived cell lines and xenograft models. We identified novel OCT4-binding sites in the MYC promoter/Cell death & diseaseMYC transcription activation mediated by OCT4 as a mechanism of resistance to 13-cisRA-mediated differentiation in neuroblastoma.PMC7224192R01 CA232591R01 CA221957R01 CA168699RP130547RP170470Yang IHReynolds CPMook DGMakena MRShimada HNguyen THWei SJVerlekar DHindle AKang MHMartinez GMYang SfalseMYC transcription activation mediated by OCT4 as a mechanism of resistance to 13-cisRA-mediated differentiation in neuroblastoma.Despite the improvement in clinical outcome with 13-cis-retinoic acid (13-cisRA) + anti-GD2 antibody + cytokine immunotherapy given in first response ~40% of high-risk neuroblastoma patients die of recurrent disease. MYCN genomic amplification is a biomarker of aggressive tumors in the childhood cancer neuroblastoma. MYCN expression is downregulated by 13-cisRA, a differentiating agent that is a component of neuroblastoma therapy. Although MYC amplification is rare in neuroblastoma at diagnosis, we report transcriptional activation of MYC medicated by the transcription factor OCT4, functionally replacing MYCN in 13-cisRA-resistant progressive disease neuroblastoma in large panels of patient-derived cell lines and xenograft models. We identified novel OCT4-binding sites in the MYC promoter/2020-01-01T00:00:00Z2020 May2025-04-19T01:47:35.994Z2020-05-22T20:21:19ZS-EPMC72241923240968510.1038/s41419-020-2563-4