ArticlePloS one2013
A p53 drug response signature identifies prognostic genes in high-risk neuroblastoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Integrative genomic analyses identify neuroblastoma risk genes involved in neuronal differentiation.Human genetics · 2024Article
- From the identification of actionable molecular targets to the generation of faithful neuroblastoma patient-derived preclinical models.Journal of translational medicine · 2024Article
- RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition.Science advances · 2022Article
- MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1.Oncology letters · 2021Article
- Restoration of the molecular clock is tumor suppressive in neuroblastoma.Nature communications · 2021Article
- Challenging, Accurate and Feasible: CAF-1 as a Tumour Proliferation Marker of Diagnostic and Prognostic Value.Cancers · 2021Review
- Association of PARP1 polymorphisms with response to chemotherapy in patients with high-risk neuroblastoma.Journal of cellular and molecular medicine · 2020Article
- Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma.Cancer communications (London, England) · 2020Article
- CHAF1A interacts with TCF4 to promote gastric carcinogenesis via upregulation of c-MYC and CCND1 expression.EBioMedicine · 2018Article
- Reversible LSD1 inhibition with HCI-2509 induces the p53 gene expression signature and disrupts the MYCN signature in high-risk neuroblastoma cells.Oncotarget · 2018Article
- p53 Nongenotoxic Activation and mTORC1 Inhibition Lead to Effective Combination for Neuroblastoma Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Application of CRISPR/Cas9 to the study of brain development and neuropsychiatric disease.Molecular and cellular neurosciences · 2017Review
- Neuroblastoma treatment in the post-genomic era.Journal of biomedical science · 2017Review
- Comparative analysis of genes frequently regulated by drugs based on connectivity map transcriptome data.PloS one · 2017Article
- Novel MDM2 inhibitor SAR405838 (MI-773) induces p53-mediated apoptosis in neuroblastoma.Oncotarget · 2016Article
- Artificial neural network classifier predicts neuroblastoma patients' outcome.BMC bioinformatics · 2016Article
- Transcript signatures that predict outcome and identify targetable pathways in MYCN-amplified neuroblastoma.Molecular oncology · 2016Article
- Contextualizing the Genes Altered in Bladder Neoplasms in Pediatric andTeen Patients Allows Identifying Two Main Classes of Biological ProcessesInvolved and New Potential Therapeutic Targets.Current genomics · 2016Article
- Chromatin assembly factor 1, subunit A (P150) facilitates cell proliferation in human hepatocellular carcinoma.OncoTargets and therapy · 2016Article
- A Potential New Mechanism of Arsenic Carcinogenesis: Depletion of Stem-Loop Binding Protein and Increase in Polyadenylated Canonical Histone H3.1 mRNA.Biological trace element research · 2015Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy induces apoptosis and tumor regression primarily through activation of p53-mediated transcription. Neuroblastoma is a p53 wild type malignancy at diagnosis and repression of p53 signaling plays an important role in its pathogenesis. Recently developed small molecule inhibitors of the MDM2-p53 interaction are able to overcome this repression and potently activate p53 dependent apoptosis in malignancies with intact p53 downstream signaling. We used the small molecule MDM2 inhibitor, Nutlin-3a, to determine the p53 drug response signature in neuroblastoma cells. In addition to p53 mediated apoptotic signatures, GSEA and pathway analysis identified a set of p53-repressed genes that were reciprocally over-expressed in neuroblastoma patients with the worst overall outcome in multiple clinical cohorts. Multifactorial regression analysis identified a subset of four genes (CHAF1A, RRM2, MCM3, and MCM6) whose expression together strongly predicted overall and event-free survival (p<0.0001). The expression of these four genes was then validated by quantitative PCR in a large independent clinical cohort. Our findings further support the concept that oncogene-driven transcriptional networks opposing p53 activation are essential for the aggressive behavior and poor response to therapy of high-risk neuroblastoma.
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