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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In conclusion, this study elucidated that combination of cisplatin and XAV-939 exerted cytotoxic and genotoxic effect to abrogate CSC mediated chemoresistance in HNSCC in synergistic manner.
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research
Publication date: Available online 17 August 2019Source: Revista Clínica Española (English Edition)Author(s): J. Masip, J.R. Germà LluchAbstractRecent epidemiological studies have shown that alcohol consumption can increase the risk of arterial hypertension, atrial fibrillation and gastrointestinal and breast cancer. Various sectors are therefore promoting abstinence from alcohol. However, light alcohol consumption has once again been shown to reduce the risk of myocardial infarction and diabetes but with an unclear effect on cerebrovascular disease. The decision to consume alcohol should therefore be ...
Source: Revista Clinica Espanola - Category: Internal Medicine Source Type: research
Publication date: Available online 17 August 2019Source: Surgery (Oxford)Author(s): Tim LaneAbstractUpper tract transitional cell carcinoma is a lethal disease with half the patients dead within 5 years of diagnosis. Unlike urothelial tumours arising in the bladder, the disease is more likely to be invasive at the time of diagnosis and in part reflects the poorer prognosis. It is a biologically aggressive disease with a high chance of recurrence even after local control. Diagnosis is made by a combination of upper tract imaging, urine cytology and ureteroscopic biopsy. Organ-confined disease is amenable to radical surgery,...
Source: Surgery (Oxford) - Category: Surgery Source Type: research
This article aims to summarize the current knowledge of prostate cancer and treatment options available.
Source: Surgery (Oxford) - Category: Surgery Source Type: research
Publication date: Available online 17 August 2019Source: Surgery (Oxford)Author(s): Jameel Mushtaq, Ramesh Thurairaja, Rajesh NairAbstractUrothelial carcinoma of the bladder is the most common malignancy affecting the urinary tract. This review examines the current standards in the diagnosis and management of this disease. Cystoscopy and urine cytology remain important tools in the diagnosis and follow-up of bladder cancer. Alternatives include photodynamic diagnosis, narrow band imaging and professional image enhancement which may improve detection of tumours. En-bloc resection using either laser or electrocautery shows p...
Source: Surgery (Oxford) - Category: Surgery Source Type: research
ConclusionsWe present the rare case of a patient with surgically resected locally advanced rectal cancer who demonstrated an impressive pCR with preoperative chemotherapy, which included FOLFOX plus bevacizumab.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
CONCLUSIONWe present a case of SCC in the anal canal with liver metastasis presenting as a hepatic pseudocyst.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
ConclusionIn this study, we found that over-expression of TINCR may influence the tumor size and contribute to the poor prognosis of cancer.
Source: Pathology Research and Practice - Category: Pathology Source Type: research
ConclusionCC shows an indolent clinical behavior, with a low recurrence rate after radical surgery. The diagnosis of this rare tumor is typically made after surgery. An aggressive approach is required with curative intents.
Source: Pathology Research and Practice - Category: Pathology Source Type: research
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Source: Neurology - Category: Neurology Authors: Tags: Neurogenetics and Ataxia Source Type: research
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