ArticleGenes & cancer2010
Gene Amplifications in Well-Differentiated Pancreatic Neuroendocrine Tumors Inactivate the p53 Pathway.
Article in Genes & cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 115 citations in OpenAlex.
- Role of advanced imaging in primary hepatic neuroendocrine tumor with borderline raised AFP and negative chromogranin staining: A case report.International journal of surgery case reports · 2024Article
- PPM1D/Wip1 is amplified, overexpressed, and mutated in human non-Hodgkin's lymphomas.Molecular biology reports · 2024Article
- An Overview of Altered Pathways Associated with Sensitivity to Platinum-Based Chemotherapy in Neuroendocrine Tumors: Strengths and Prospects.International journal of molecular sciences · 2024Review
- Functional Copy-Number Alterations as Diagnostic and Prognostic Biomarkers in Neuroendocrine Tumors.International journal of molecular sciences · 2024Article
- MDMX in Cancer: A Partner of p53 and a p53-Independent Effector.Biologics : targets & therapy · 2024Review
- Neuroendocrine Tumors: Genomics and Molecular Biomarkers with a Focus on Metastatic Disease.Cancers · 2023Review
- PPM1D in Solid and Hematologic Malignancies: Friend and Foe?Molecular cancer research : MCR · 2022Article
- Context matters - Daxx and Atrx are not robust tumor suppressors in the murine endocrine pancreas.Disease models & mechanisms · 2022Article
- The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms.Cancer science · 2022Article
- Review
- From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?Reviews in endocrine & metabolic disorders · 2021Review
- Molecular Pathology of Well-Differentiated Gastro-entero-pancreatic Neuroendocrine Tumors.Endocrine pathology · 2021Review
- Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? - A preclinical assessment in vitro and in vivo.Neoplasia (New York, N.Y.) · 2021Article
- Pancreatic neuroendocrine neoplasms: current state and ongoing controversies on terminology, classification and prognostication.Journal of gastrointestinal oncology · 2020Review
- Molecular drivers and cells of origin in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine carcinoma.Experimental hematology & oncology · 2020Review
- PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma.Nature communications · 2019Article
- Insights into the biology and treatment strategies of pancreatic neuroendocrine tumors.Annals of pancreatic cancer · 2019Article
- Pancreatic neuroendocrine tumor, lymphoma, and squamous cell carcinoma of hypopharynx; A case report of three primary cancers in one patient.International journal of surgery case reports · 2019Article
- Protein Phosphatase Magnesium-Dependent 1δ (PPM1D) Expression as a Prognostic Marker in Adult Supratentorial Diffuse Astrocytic and Oligodendroglial Tumors.Journal of pathology and translational medicine · 2018Article
- The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines.Endocrine-related cancer · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Neuroendocrine tumors (NETs) comprise a group of rare tumors derived from the diffuse neuroendocrine system or islet endocrine cells of the pancreas. The molecular mechanisms underlying NETs are largely unknown. The tumor suppressor p53 plays a critical role in maintaining genomic stability and tumor prevention. The p53 pathway is tightly regulated by a number of proteins, among which MDM2, MDM4, and WIP1 are key negative regulators of p53 protein levels or activity. Aberrant activation of these negative regulators can attenuate the p53 function that serves as an important mechanism of tumorigenesis. In this study, several genetic alterations in pancreatic NETs were studied. These tumors exhibit various chromosomal aberrations throughout the whole genome as examined by array-based comparative genomic hybridization. Although p53 mutations are rare in NETs (<3%), this study presents evidence that the p53 pathway is altered in pancreatic NETs through aberrant activation of its negative regulators. A high percentage of pancreatic NETs contain extra gene copies of MDM2 (22%), MDM4 (30%), and WIP1 (51%), which are correlated with expression of corresponding mRNAs and proteins. In addition, there is a higher frequency (23% v. 15% in the control population) of the G/G genotype of MDM2 SNP309, a functional single-nucleotide polymorphism in the MDM2 gene that attenuates the function of the p53 protein. Overall, approximately 70% of pancreatic NETs have one or more of these genetic changes. These findings suggest that the negative regulation of p53 function could be an important mechanism for the initiation and/or progression of pancreatic NETs, and reactivation of p53 could be a potential therapeutic strategy for patients with this disease.
Identifiers
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Registered trials
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.