ArticleNeoplasia (New York, N.Y.)2013
Stress-induced isoforms of MDM2 and MDM4 correlate with high-grade disease and an altered splicing network in pediatric rhabdomyosarcoma.
Article in Neoplasia (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Employing splice-switching oligonucleotides and AAVrh74.U7 snRNA to target insulin receptor splicing and cancer hallmarks in osteosarcoma.Molecular therapy. Oncology · 2024Article
- MDM4 was associated with poor prognosis and tumor-immune infiltration of cancers.European journal of medical research · 2024Article
- Alternative RNA splicing defects in pediatric cancers: new insights in tumorigenesis and potential therapeutic vulnerabilities.Annals of oncology : official journal of the European Society for Medical Oncology · 2022Review
- Splice-switching of the insulin receptor pre-mRNA alleviates tumorigenic hallmarks in rhabdomyosarcoma.NPJ precision oncology · 2022Article
- Mdm2 and MdmX RING Domains Play Distinct Roles in the Regulation of p53 Responses: A Comparative Study of Mdm2 and MdmX RING Domains in U2OS Cells.International journal of molecular sciences · 2020Article
- MDM2-C Functions as an E3 Ubiquitin Ligase.Cancer management and research · 2020Article
- Genome-wide profiling of prognosis-related alternative splicing signatures in sarcoma.Annals of translational medicine · 2019Article
- Determining the prognostic significance of alternative splicing events in soft tissue sarcoma using data from The Cancer Genome Atlas.Journal of translational medicine · 2019Article
- A novel mouse model of rhabdomyosarcoma underscores the dichotomy of MDM2-ALT1 function in vivo.Oncogene · 2018Article
- The Role of MDM2 in Promoting Genome Stability versus Instability.International journal of molecular sciences · 2017Review
- Mutant p53 in Cancer: Accumulation, Gain-of-Function, and Therapy.Journal of molecular biology · 2017Review
- Alternative splicing of spleen tyrosine kinase differentially regulates colorectal cancer progression.Oncology letters · 2016Article
- Aberrant splicing of the DMP1-ARF-MDM2-p53 pathway in cancer.International journal of cancer · 2016Review
- The Roles of MDM2 and MDMX in Cancer.Annual review of pathology · 2016Review
- Splicing factor SRSF1 negatively regulates alternative splicing of MDM2 under damage.Nucleic acids research · 2015Article
- Alternative splicing of MEF2C pre-mRNA controls its activity in normal myogenesis and promotes tumorigenicity in rhabdomyosarcoma cells.The Journal of biological chemistry · 2015Article
- The splicing factor FUBP1 is required for the efficient splicing of oncogene MDM2 pre-mRNA.The Journal of biological chemistry · 2014Article
- Stress-induced alternative splice forms of MDM2 and MDMX modulate the p53-pathway in distinct ways.PloS one · 2014Article
- Cancer subclonal genetic architecture as a key to personalized medicine.Neoplasia (New York, N.Y.) · 2013Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Pediatric rhabdomyosarcoma (RMS) is a morphologically and genetically heterogeneous malignancy commonly classified into three histologic subtypes, namely, alveolar, embryonal, and anaplastic. An issue that continues to challenge effective RMS patient prognosis is the dearth of molecular markers predictive of disease stage irrespective of tumor subtype. Our study involving a panel of 70 RMS tumors has identified specific alternative splice variants of the oncogenes Murine Double Minute 2 (MDM2) and MDM4 as potential biomarkers for RMS. Our results have demonstrated the strong association of genotoxic-stress inducible splice forms MDM2-ALT1 (91.6% Intergroup Rhabdomyosarcoma Study Group stage 4 tumors) and MDM4-ALT2 (90.9% MDM4-ALT2-positive T2 stage tumors) with high-risk metastatic RMS. Moreover, MDM2-ALT1-positive metastatic tumors belonged to both the alveolar (50%) and embryonal (41.6%) subtypes, making this the first known molecular marker for high-grade metastatic disease across the most common RMS subtypes. Furthermore, our results show that MDM2-ALT1 expression can function by directly contribute to metastatic behavior and promote the invasion of RMS cells through a matrigel-coated membrane. Additionally, expression of both MDM2-ALT1 and MDM4-ALT2 increased anchorage-independent cell-growth in soft agar assays. Intriguingly, we observed a unique coordination in the splicing of MDM2-ALT1 and MDM4-ALT2 in approximately 24% of tumor samples in a manner similar to genotoxic stress response in cell lines. To further explore splicing network alterations with possible relevance to RMS disease, we used an exon microarray approach to examine stress-inducible splicing in an RMS cell line (Rh30) and observed striking parallels between stress-responsive alternative splicing and constitutive splicing in RMS tumors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.