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

Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often occurs in middle aged patients. Clinically, it is challenging to distinguish A3 from glioblastoma multiforme (GBM) WHO grade IV. To reveal the genetic landscape of this tumor type, we sequenced the exome of a cohort of A3s (n=16). For comparison and to illuminate the genomic landscape of other glioma subtypes, we also included in our study diffuse astrocytoma WHO grade II (A2, n=7), oligoastrocytoma WHO grade II (OA2, n=2), anaplastic oligoastrocytoma WHO grade III (OA3, n=4), and GBM (n=28). Exome sequencing of A3s identified frequent mutations in IDH1 (75%, 12/16), ATRX (63%, 10/16), and TP53 (82%, 13/16). In contrast, the majority of GBMs (75%, 21/28) did not contain IDH1 or ATRX mutations, and displayed a distinct spectrum of mutations. Finally, our study also identified novel genes that were not previously linked to this tumor type. In particular, we found mutations in Notch pathway genes (NOTCH1, NOTCH2, NOTCH4, NOTCH2NL), including a recurrent NOTCH1-A465Tmutation, in 31% (5/16) of A3s. This study suggests genetic signatures will be useful for the classification of gliomas.
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PMID:The genetic landscape of anaplastic astrocytoma. 2414 May 81

Based on the assumption that apparent diffusion coefficients (ADCs) define high-risk clinical target volume (aCTVHR) in high-grade glioma in a cellularity-dependent manner, the dosimetric effects of aCTVHR-targeted dose optimization were evaluated in two intensity-modulated radiation therapy (IMRT) plans. Diffusion-weighted magnetic resonance (MR) images and ADC maps were analyzed qualitatively and quantitatively to determine aCTVHR in a high-grade glioma with high cellularity. After confirming tumor malignancy using the average and minimum ADCs and ADC ratios, the aCTVHR with double- or triple-restricted water diffusion was defined on computed tomography images through image registration. Doses to the aCTVHR and CTV defined on T1-weighted MR images were optimized using a simultaneous integrated boost technique. The dosimetric benefits for CTVs and organs at risk (OARs) were compared using dose volume histograms and various biophysical indices in an ADC map-based IMRT (IMRTADC) plan and a conventional IMRT (IMRTconv) plan. The IMRTADC plan improved dose conformity up to 15 times, compared to the IMRTconv plan. It reduced the equivalent uniform doses in the visual system and brain stem by more than 10% and 16%, respectively. The ADC-based target differentiation and dose optimization may facilitate conformal dose distribution to the aCTVHR and OAR sparing in an IMRT plan.
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PMID:Dosimetric Effects of Magnetic Resonance Imaging-assisted Radiotherapy Planning: Dose Optimization for Target Volumes at High Risk and Analytic Radiobiological Dose Evaluation. 2642 53