Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic gliomas. We also performed targeted mutational analysis of an additional 24 such tumors and genome-wide methylation profiling of 45 gliomas. This study led to the discovery of tumor-specific mutations in PPM1D, encoding wild-type p53-induced protein phosphatase 1D (WIP1), in 37.5% of the BSGs that harbored hallmark H3F3A mutations encoding p.Lys27Met substitutions. PPM1D mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53 activation in vitro. PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2. These results define PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas.
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PMID:Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas. 2488 Mar 41

p53-induced protein with a RING-H2 domain (Pirh2), also known as Rchy1, is an ubiquitin E3 ligase that regulates the turnover and functionality of several proteins involved in cell proliferation and differentiation, cell cycle checkpoints, and cell death. However, it remains unclear whether aberrant expression of Pirh2 is involved in the development of glioma, a major type of primary brain tumor in adults. Western blot and immunohistochemical analyses showed that Pirh2 was highly expressed in glioma specimens, compared with normal brain tissues. High Pirh2 expression was positively correlated with higher tumor grade, as well as Ki-67 expression. Kaplan-Meier analysis revealed that patients with high Pirh2 expression had worsened prognosis, compared with those with low Pirh2 expression. Moreover, to determine whether Pirh2 could regulate malignant behavior of glioma cells, we transfected glioma cells with interfering RNA targeting Pirh2 to specifically silence Pirh2 expression. Mechanistically, our results indicated that knockdown of Pirh2 induced the apoptosis of glioma cells. In addition, depletion of Pirh2 diminished the expression of PCNA and cyclin D1 and led to cell cycle arrest at G1 phase. Taken together, these findings for the first time suggest that Pirh2 might play an important role in the regulation of glioma proliferation and apoptosis and thus serve as a promising therapeutic target in the treatment of glioma.
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PMID:High Expression of Pirh2 is Associated with Poor Prognosis in Glioma. 2825 14