Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P31749 (AKT)
 22,954 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pediatric gliomas comprise a clinically, histologically, and molecularly very heterogeneous group of CNS tumors. In addition, these tumors are largely different from their counterparts occurring in adults, although they are histologically indistinguishable and uniformly classified by the current WHO classification for CNS tumors. Pilocytic astrocytoma (WHO grade I), mainly arising in the posterior fossa, is the most common representative in children, whereas glioblastoma multiforme (WHO grade IV) predominates in adults. When radical surgical resection is possible in low-grade gliomas, it will likely cure the patient. If complete surgical resection is not possible, however, for example in brainstem gliomas, which are defined by their anatomic localization rather than by their histological or molecular features, therapeutic options are limited and prognosis is usually poor. Recent genome-wide analyses applying different microarray-based methods to investigate DNA copy-number aberrations, mRNA expression signatures, and methylation patterns have shed some light on the pathways involved in the pathogenesis of pediatric glio-mas. Mitogen-activated protein kinase (MAPK) and PI3K/AKT signaling were identified as prominent oncogenic pathways in astrocytic tumors in several studies, whereas NOTCH signaling was implicated in the pathogenesis of a subset of intracranial ependymomas. Future therapeutic strategies targeting these (and other) pathways or conferring epigenetic modifications in the tumor might contribute to a better treatment outcome of patients with unresectable or disseminated tumors at diagnosis. Consideration of reliable molecular markers for outcome prediction will most likely result in a better stratification of patients into different risk groups with adjusted treatment intensity in the future.
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PMID:Pediatric gliomas. 1932 38

Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic condition characterized by ocular, cutaneous, and central nervous system anomalies. Key clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, and central nervous system lipomas. Seizures, spasticity, and intellectual disability can be present, although affected individuals without seizures and with normal intellect have also been reported. Given the patchy and asymmetric nature of the malformations, ECCL has been hypothesized to be due to a post-zygotic, mosaic mutation. Despite phenotypic overlap with several other disorders associated with mutations in the RAS-MAPK and PI3K-AKT pathways, the molecular etiology of ECCL remains unknown. Using exome sequencing of DNA from multiple affected tissues from five unrelated individuals with ECCL, we identified two mosaic mutations, c.1638C>A (p.Asn546Lys) and c.1966A>G (p.Lys656Glu) within the tyrosine kinase domain of FGFR1, in two affected individuals each. These two residues are the most commonly mutated residues in FGFR1 in human cancers and are associated primarily with CNS tumors. Targeted resequencing of FGFR1 in multiple tissues from an independent cohort of individuals with ECCL identified one additional individual with a c.1638C>A (p.Asn546Lys) mutation in FGFR1. Functional studies of ECCL fibroblast cell lines show increased levels of phosphorylated FGFRs and phosphorylated FRS2, a direct substrate of FGFR1, as well as constitutive activation of RAS-MAPK signaling. In addition to identifying the molecular etiology of ECCL, our results support the emerging overlap between mosaic developmental disorders and tumorigenesis.
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PMID:Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis. 2694 90

Recent investments in research associated with the discovery of specific tumor biomarkers important for efficient diagnosis and prognosis are beginning to bear fruit. Key biomarkers could potentially outweigh traditional radiological or pathological methods by enabling specificity of early detection, when coupled with tumor molecular profiling and clinical associations. Only few biomarkers are approved by regulatory authorities for Central Nervous System Tumors (CNSTs), despite the evaluation of a large number of CNST related markers during clinical trials. Traditional CNSTs biomarkers include 1p/19q co-deletion, O6-Methylguanine-DNA Methyltransferase Methylation, and mutations in IDH1/IDH2. Recently tested CNSTs biomarkers include VEGFR-2, EGFRvIII, IL2, PDGFR, MMPs, BRAF, STAT3, PTEN, TERT, AKT, NF2, and BCL2. Additional studies have highlighted new and novel MicroRNAs, circular RNAs and long non-coding RNAs as promising biomarkers. Studies on microvesicles pinpoint exosomes as promising, less invasive biomarkers that could be isolated from the serum of cancer patients. Furthermore, Cancer Stem Cells (CSCs) related molecules, such as CD133, SOX2 and Nestin, utilized as CNST biomarkers, might enable efficient monitoring of cancer progression, and/or surveillance of emerging drug resistant cells. Approved protocols that implement novel molecular markers in diagnostics, prognostics and drug development will herald a new era of precision and personalized neuro-oncology. This review summarizes and discusses putative CNST biomarkers that are under clinical development, and are ready to move into diagnostic, prognostic and therapeutic applications. Data presented here is predicted to aid in streamlining the process of biomarker's research and development.
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PMID:Current and emerging biomarkers in tumors of the central nervous system: Possible diagnostic, prognostic and therapeutic applications. 2877 35