PDGFRA Mutations in Gliomagenesis

The outcome for children with high-grade gliomas (HGG) remains dismal, with a 2-year survival rate of only 10% to 30%. Diffuse intrinsic pontine glioma (DIPG) comprise a subset of HGG that arise in the brainstem almost exclusively in children. Genome-wide analyses of copy number imbalances previously showed that platelet-derived growth factor receptor α (PDGFRA) is the most frequent target of focal amplification in pediatric HGGs, including DIPGs. To determine whether PDGFRA is also targeted by more subtle mutations missed by copy number analysis, we sequenced all PDGFRA coding exons from a cohort of pediatric HGGs. Somatic-activating mutations were identified in 14.4% (13 of 90) of nonbrainstem pediatric HGGs and 4.7% (2 of 43) of DIPGs, including missense mutations and in-frame deletions and insertions not previously described. Forty percent of tumors with mutation showed concurrent amplification, whereas 60% carried heterozygous mutations. Six different mutations impacting different domains all resulted in ligand-independent receptor activation that was blocked by small molecule inhibitors of PDGFR. Expression of mutants in p53-null primary mouse astrocytes conferred a proliferative advantage in vitro and generated HGGs in vivo with complete penetrance when implanted into brain. The gene expression signatures of these murine HGGs reflected the spectrum of human diffuse HGGs. PDGFRA intragenic deletion of exons 8 and 9 were previously shown in adult HGG, but were not ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Pathobiology Source Type: research

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ConclusionDifferentially expressed in tumors, PLA2G4A, PRKCB, PIK3R1, KDR, PLA2G1B and PTGS2 are potential therapeutic targets of Yupingfengsan in the treatment of LAD, and MAPK, VEGF and ErbB signaling pathways are involved.
Source: European Journal of Integrative Medicine - Category: Complementary Medicine Source Type: research
Publication date: Available online 21 August 2019Source: Seminars in Cancer BiologyAuthor(s): Btissame El Hassouni, Carlotta Granchi, Andrea Vallés-Martí, I Gede Putu Supadmanaba, Giulia Bononi, Tiziano Tuccinardi, Niccola Funel, Connie R. Jimenez, Godefridus J. Peters, Elisa Giovannetti, Filippo MinutoloAbstractCancer metastasis to distant organs is initiated by tumor cells that disseminate from primary heterogeneous tumors. The subsequent growth and survival of tumor metastases depend on different metabolic changes, which constitute one of the enigmatic properties of tumor cells. Aerobic glycolysis, ‘...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 21 August 2019Source: Seminars in Cancer BiologyAuthor(s): Yue Zhao, Jiahui Li, Dai Li, Zhefang Wang, Jiangang Zhao, Xiaolin Wu, Qiye Sun, Peter Ping Lin, Patrick Plum, Menglong Zhou, Zhen Zhang, Hans Schlösser, Peter J. Nelson, Christiane J. BrunsAbstractMore than 70% of gastrointestinal (GI) cancers are diagnosed with metastases, leading to poor prognosis. For some cancer patients with limited sites of metastatic tumors, the term oligometastatic disease (OMD) has been coined as opposed to systemic polymetastasis (PMD) disease. Stephan Paget first described an organ-specific pattern...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 21 August 2019Source: Seminars in Cancer BiologyAuthor(s): Francesco Spagnolo, Andrea Boutros, Enrica Tanda, Paola QueiroloAbstractThe past 5 years have witnessed the results of many practice-changing studies that have dramatically improved the landscape of adjuvant therapy in patients with resected, high-risk melanoma. After a 20-year era of adjuvant interferon, the anti-CTLA-4 and anti-PD-1 immune-checkpoint inhibitors, and MAPK-directed targeted therapy brought a revolution into the adjuvant treatment of melanoma. These results came along with the practice-changing results of two large...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 21 August 2019Source: Seminars in Cancer BiologyAuthor(s): Carlos S. MorenoAbstractSOX4 is an essential developmental transcription factor that regulates stemness, differentiation, progenitor development, and multiple developmental pathways including PI3K, Wnt, and TGFβ signaling. The SOX4 gene is frequently amplified and overexpressed in over 20 types of malignancies, and multiple lines of evidence support that notion that SOX4 is an oncogene. Its overexpression is due to both gene amplification and to activation of PI3K, Wnt, and TGFβ pathways that SOX4 regulates. SOX4 interac...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
This article reviews endogenous- and exogenous-based stimulus-responsive drug delivery systems designed to overcome the limitations of conventional therapies. The article also summarizes the study of nanomaterials, including polymeric, gold, silver, magnetic, and quantum dot nanoparticles. Though an array of drug delivery systems has so far been proposed, there remain many challenges and concerns that should be addressed in order to fill the gaps in the field. Prominence is given to drug delivery systems that employ external- and internal-based stimuli and that are emerging as promising tools for cancer therapeutics in clinical settings.
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 21 August 2019Source: Journal of Geriatric OncologyAuthor(s): Guillaume Beinse, Delphine Reitter, Lauriane Segaux, Muriel Carvahlo-Verlinde, Benoit Rousseau, Christophe Tournigand, Tristan Cudennec, Marie Laurent, Pascaline Boudou-Rouquette, Elena Paillaud, Florence Canouï-Poitrine, Philippe Caillet, for the ELCAPA Study GroupAbstractBackgroundBecause of comorbidities and polypharmacy, older patients with cancer have a greater risk of iatrogenic events. We aimed to characterize potential drug-drug interactions (PDIs) and the risk of unplanned hospitalization in older patients with ca...
Source: Journal of Geriatric Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 21 August 2019Source: Cancer GeneticsAuthor(s): Nicoletta Coccaro, Luisa Anelli, Paola Orsini, Antonella Zagaria, Angela Minervini, Luciana Impera, Giuseppina Tota, Crescenzio Francesco Minervini, Cosimo Cumbo, Elisa Parciante, Maria Rosa Coserva, Immacolata Attolico, Giorgina Specchia, Francesco AlbanoAbstractMyeloid neoplasms with eosinophilia and abnormalities of the PDGFRA gene can benefit from therapy with tyrosine kinase inhibitors, therefore revealing the PDGFRA rearrangement is essential to ensure the best choice of treatment. The most common PDGFRA partner is the FIP1L1 gene, gen...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research
ConclusionPPI use was associated with an increased risk of gastric and oesophageal cancer and the risk remained increased over follow-up. These results support our original hypothesis that use of PPIs may be a risk factor for gastric and oesophageal cancer in the general population of maintenance users, independent of underlying indications.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: In patients with NF I hydrocephalus can be caused by different types of lesions but uniquely it can also be of unknown etiology and without any clinical symptoms or signs. 1. A. Dincer. Hydrocephalus in patients with neurofibromatosis type 1: MR imaging findings and the outcome of endoscopic third ventriculostomy. American Journal of Neuroradiology 2. Creange, A. Neurological complications of neurofibromatosis type 1 in adulthood. Brain. Journal of Neurology. Oct 1998. Volume 122, Issue 3, pp473-481Disclosure: Dr. Elgallab has nothing to disclose. Dr. Graber has received personal compensation for activities wi...
Source: Neurology - Category: Neurology Authors: Tags: Neurogenetics and Ataxia Source Type: research
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