Characterisation of isocitrate dehydrogenase 1/isocitrate dehydrogenase 2 gene mutation and the d ‐2‐hydroxyglutarate oncometabolite level in dedifferentiated chondrosarcoma

2020 ◽  
Vol 76 (5) ◽  
pp. 722-730 ◽  
Author(s):  
Nissreen Mohammad ◽  
Derek Wong ◽  
Amy Lum ◽  
Jonah Lin ◽  
Julie Ho ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Isocitrate Dehydrogenase ◽  
Dedifferentiated Chondrosarcoma ◽  
Isocitrate Dehydrogenase 1 ◽  
Isocitrate Dehydrogenase 2

scholarly journals Computational Analysis of IDH1, IDH2, and TP53 Mutations in Low-Grade Gliomas Including Oligodendrogliomas and Astrocytomas

2020 ◽  
Vol 19 ◽  
pp. 117693512091583 ◽  
Author(s):  
Mohammed Amine Bendahou ◽  
Housna Arrouchi ◽  
Wiame Lakhlili ◽  
Loubna Allam ◽  
Tarik Aanniz ◽  
...  
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Computational Analysis ◽  
Catalytic Site ◽  
Dimensional Structure ◽  
Low Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Modeling Tools ◽  
Low Grade Gliomas ◽  
Isocitrate Dehydrogenase 2 ◽  
The Impact

Introduction: The emergence of new omics approaches, such as genomic algorithms to identify tumor mutations and molecular modeling tools to predict the three-dimensional structure of proteins, has facilitated the understanding of the dynamic mechanisms involved in the pathogenesis of low-grade gliomas including oligodendrogliomas and astrocytomas. Methods: In this study, we targeted known mutations involved in low-grade gliomas, starting with the sequencing of genomic regions encompassing exon 4 of isocitrate dehydrogenase 1 ( IDH1) and isocitrate dehydrogenase 2 ( IDH2) and the four exons (5-6 and 7-8) of TP53 from 32 samples, followed by computational analysis to study the impact of these mutations on the structure and function of 3 proteins IDH1, IDH2, and p53. Results: We obtain a mutation that has an effect on the catalytic site of the protein IDH1 as R132H and on the catalytic site of the protein IDH2 as R172M. Other mutations at p53 have been identified as K305N, which is a pathogenic mutation; R175 H, which is a benign mutation; and R158G, which disrupts the structural conformation of the tumor suppressor protein. Conclusion: In low-grade gliomas, mutations in IDH1, IDH2, and TP53 may be the key to tumor progression because they have an effect on the function of the protein such as mutations R132H in IDH1 and R172M in IDH2, which change the function of the enzyme alpha-ketoglutarate, or R158G in TP53, which affects the structure of the generated protein, thus their importance in understanding gliomagenesis and for more accurate diagnosis complementary to the anatomical pathology tests.

scholarly journals Isocitrate dehydrogenase 1 Gene Mutation Is Associated with Prognosis in Clinical Low-Grade Gliomas

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130872 ◽  
Author(s):  
Ming-Yang Li ◽  
Yin-Yan Wang ◽  
Jin-Quan Cai ◽  
Chuan-Bao Zhang ◽  
Kuan-Yu Wang ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Isocitrate Dehydrogenase ◽  
Low Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Low Grade Gliomas

Spinal Cord Astrocytoma with Isocitrate Dehydrogenase 1 Gene Mutation

2017 ◽  
Vol 108 ◽  
pp. 991.e13-991.e16 ◽  
Author(s):  
Keisuke Takai ◽  
Shota Tanaka ◽  
Takashi Sota ◽  
Akitake Mukasa ◽  
Takashi Komori ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Mutation ◽  
Isocitrate Dehydrogenase ◽  
Isocitrate Dehydrogenase 1 ◽  
Spinal Cord Astrocytoma

scholarly journals IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma

Blood ◽  
2012 ◽  
Vol 119 (8) ◽  
pp. 1901-1903 ◽  
Author(s):  
Rob A. Cairns ◽  
Javeed Iqbal ◽  
François Lemonnier ◽  
Can Kucuk ◽  
Laurence de Leval ◽  
...  
Keyword(s):  
T Cell ◽  
Isocitrate Dehydrogenase ◽  
Cell Lymphoma ◽  
Independent Set ◽  
T Cell Lymphoma ◽  
Large Set ◽  
Isocitrate Dehydrogenase 1 ◽  
T Cell Lymphomas ◽  
Isocitrate Dehydrogenase 2 ◽  
Arginine Residues

Abstract Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in most grade 2 and 3 gliomas, secondary glioblastomas, and a subset of acute myelogenous leukemias but have not been detected in other tumor types. The mutations occur at specific arginine residues and result in the acquisition of a novel enzymatic activity that converts 2-oxoglutarate to D-2-hydroxyglutarate. This study reports IDH1 and IDH2 genotyping results from a set of lymphomas, which included a large set of peripheral T-cell lymphomas. IDH2 mutations were identified in approximately 20% of angioimmunoblastic T-cell lymphomas (AITLs), but not in other peripheral T-cell lymphoma entities. These results were confirmed in an independent set of AITL patients, where the IDH2 mutation rate was approximately 45%. This is the second common genetic lesion identified in AITL after TET2 and extends the number of neoplastic diseases where IDH1 and IDH2 mutations may play a role.

scholarly journals Somatic IDH1 mutation in a pituitary adenoma of a patient with Maffucci syndrome

2016 ◽  
Vol 124 (6) ◽  
pp. 1562-1567 ◽  
Author(s):  
Shuyu Hao ◽  
Christopher S. Hong ◽  
Jie Feng ◽  
Chunzhang Yang ◽  
Prashant Chittiboina ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Dna Sequencing ◽  
Isocitrate Dehydrogenase ◽  
Pituitary Adenomas ◽  
Somatic Mosaicism ◽  
Intracranial Tumors ◽  
Isocitrate Dehydrogenase 1 ◽  
Maffucci Syndrome ◽  
Suprasellar Region ◽  
Isocitrate Dehydrogenase 2

Maffucci syndrome is a rare disease characterized by multiple enchondromas and soft-tissue hemangiomas. Additionally, neuroendocrine tumors including pituitary adenomas have been described in these patients. The underlying genetic etiology lies in somatic mosaicism of mutations in isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). This report describes a patient with Maffucci syndrome who presented with intracranial tumors of the skull base and suprasellar region. The patient underwent resection of both intracranial tumors, revealing histopathological diagnoses of chondrosarcoma and pituitary adenoma. DNA sequencing of the tumors was performed to identify common IDH1/2 mutations. Clinical, radiological, and biochemical assessments were performed. Genotypic studies used standard Sanger sequencing in conjunction with a target-specific peptide nucleic acid to detect IDH1 mutations in tumor tissues. DNA sequencing demonstrated identical IDH1 mutations (c.394C > T) in both tumors. To the authors’ knowledge, this report provides the first genetic evidence for the inclusion of pituitary adenomas among tumors characterizing Maffucci syndrome. In patients who are newly diagnosed with Maffucci syndrome, it is appropriate to monitor for development of pituitary pathology and neuroendocrine dysfunction.

Structural analysis of oncogenic mutation of isocitrate dehydrogenase 1

2016 ◽  
Vol 12 (7) ◽  
pp. 2276-2287 ◽  
Author(s):  
Vidya Rajendran
Keyword(s):  
Structural Analysis ◽  
Isocitrate Dehydrogenase ◽  
Isocitrate Dehydrogenase 1 ◽  
Oncogenic Mutation

Arginine to histidine mutation at position 132 (R132H) in isocitrate dehydrogenase 1 (IDH1) led to reduced affinity of the respective enzymes for isocitrate and increased affinity for α-ketoglutarate (AKG) and NADPH.

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