Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.41 (isocitrate dehydrogenase)
 3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to identify genetic and epigenetic alterations involved in the progression of oligodendroglial tumors. We characterized 21 paired, World Health Organization (WHO) grade II and III oligodendroglial tumors from patients who received craniotomies for the partial or complete resection of primary and secondary oligodendroglial tumors. Tumor DNA was analyzed for alterations in selected genetic loci (1p36, 9p22, 10q23-24, 17p13, 19q13, 22q12), isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2) and the CpG island methylation status of critical tumor-related genes (MGMT, P16, DAPK, PTEN, RASSF1A, Rb1). Alterations of these markers were common early in the tumorigenesis. In the primary tumors we identified 12 patients (57.1%) with 1p36 deletions, 17 (81.0%) with 19q13 deletions, 9 (42.9%) with 1p36/19q13 codeletions, 11 (52.3%) with 9p22 deletions, and 12 (57.1%) with IDH1 mutation. Epigenetic analysis detected promoter methylation of the MGMT, P16, DAPK, PTEN, RASSF1A, and Rb1 genes in 38.1%, 19.0%, 38.1%, 33.3%, 66.7%, and 14.3% of primary tumors, respectively. After progression, additional losses of 1p, 9p, 10q, 17p, 19q and 22q were observed in 3 (14.3%), 1 (4.8%), 3 (14.3%), 2 (9.5%), 1 (4.8%) and 3 (14.3%) cases, respectively. Additional methylations of the MGMT, P16, DAPK, PTEN, RASSF1A, and RB1 promoters was observed in 4 (19.0%), 2 (9.5%), 0 (0%), 6 (28.6%), 2(9.5%) and 3 (14.3%) cases, respectively. The status of IDH1 mutation remained unchanged in all tumors after progression. The primary tumors of three patients with subsequent progression to high-grade astrocytomas, all had 9p deletion, intact 1p, intact 10q and unmethylated MGMT. Whether this may represent a molecular signature of patients at-risk for the development of aggressive astrocytomas needs further investigation.
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PMID:Genetic and epigenetic alterations in primary-progressive paired oligodendroglial tumors. 2382 16

Promoter methylation of P15, P16, RB transcriptional corepressor 1 (RB1) and O-6-methylguanine-DNA methyltransferase (MGMT) impacts the prognosis of numerous glioma subtypes. However, whether promoter methylation of these genes also has an impact on the clinical course of pilocytic astrocytoma remains unclear. Using methylation-specific polymerase chain reaction, the methylation status of the tumor suppressor genes P15, P16, RB1, and MGMT in pilocytic astrocytomas (n=18) was analyzed. Immunohistochemical staining for the R132H mutation of the isocitrate dehydrogenase (NADP(+)) 1, cytosolic (IDH1) gene was performed. Clinical data including age, gender, localization of tumor, extent of resection, treatment modality, progression-free survival and overall survival were collected. The methylation index for P15, P16, RB1 and MGMT was 0.0, 0.0, 5.6% (1/18) and 44.5% (8/18), respectively. If the MGMT promoter was methylated, the probability of relapse and second subsequent therapy was significantly increased (P=0.019). The one patient with methylation of P15 demonstrated a poor clinical course. The pilocytic astrocytomas of all 18 patients revealed wild-type IDH1. Clinically, there was a significant correlation of subtotal resection with the occurrence of relapse (P=0.005) and of the localization of the tumor with the extent of resection (P=0.031). Gross total resection was achieved significantly more often in pediatric patients than in adult patients (P=0.003). Adult patients demonstrated more relapses following the first tumor resection (P=0.001). The present study indicates that methylation of MGMT is associated with a poor clinical course and represents an age-independent risk factor for an unfavorable outcome. Other influential factors of outcome were the age of the patient and extent of resection.
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PMID:Promoter methylation of RB1, P15, P16, and MGMT and their impact on the clinical course of pilocytic astrocytomas. 2943 55