Determining IDH-Mutational Status in Gliomas Using IDH1-R132H Antibody and Polymerase Chain Reaction

Gondim, Dibson D.; Gener, Melissa; Curless, Kendra; Cohen-Gadol, Aaron; Hattab, Eyas M.; Cheng, Liang

doi:10.1097/pai.0000000000000702

Cited by 23 publications

(22 citation statements)

References 22 publications

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“…Antibodies specific for the products of IDH1 R132H mutation may be of sufficient value of screening tool to replace more formal mutational analysis [33,34].…”

Section: Discussionmentioning

confidence: 99%

Molecular classification of diffuse gliomas

Jakovlevs¹,

Vanags²,

Gardovskis³

et al. 2019

pjp

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In this study we assessed whether gliomas could be subdivided into different molecular subtypes by immunohistochemistry (IHC) reminiscent of those first described by Verhaak et al. in 2010 (classical, proneural, mesenchymal and neural). We also evaluated the prognostic significance of single molecular factors and searched for significant correlations between markers. In this study, we included 146 patients with glioblastomas (GBMs) and 26 with diffuse astrocytomas (DAs). The glioma samples were tested for PDGFRA, IDH1 R132H, CD44, p53, Ki-67, p21 and p27 expression. We found that gliomas could be subdivided into molecular subtypes by IHC. Fifty per cent of GBMs were of the proneural subtype, 18.5% of mesenchymal subtype and 31.5% were not otherwise classified. However, most of the DAs (92.3%) belonged to the proneural subtype. No prognostic role was found for the molecular subtypes, but predictive roles were noted. Both proneural and mesenchymal molecular subtypes showed a benefit from the addition of chemotherapy and radiotherapy; however, the mesenchymal subtype showed a greater response. Interestingly, the mesenchymal subtype did not receive any benefit from the addition of radiotherapy compared with palliative management and surgery alone. Regarding single molecular markers, only IDH1 R132H was found to have a prognostic role for GBMs. There was a trend towards better survival in tumours with lower PDGFRA expression (p = 0.066). In DAs, PDGFRA and Ki-67 expression had prognostic roles. The following statistically significant correlations were found in GBMs: Ki-67/p53, Ki-67/p27 and p53/PDGFRA; in DAs: p53/ PDGFRA, CD44/PDGFRA, and p21/PDGFRA.

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“…Antibodies specific for the products of IDH1 R132H mutation may be of sufficient value of screening tool to replace more formal mutational analysis [33,34].…”

Section: Discussionmentioning

confidence: 99%

Molecular classification of diffuse gliomas

Jakovlevs¹,

Vanags²,

Gardovskis³

et al. 2019

pjp

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“…Post-operative immunohistochemistry staining and sequencing have been widely used to detect IDH mutation [ 4 , 5 ]. Intra-operative diagnosis has being well developed by Gas chromatography-mass spectrometry (GC-MS) [ 6 , 7 ], Liquid chromatography-mass spectrometry (LC-MS) [ 8 ], or antibody labelling technique [ 9 ] with adequate specificity and sensitivity.…”

Section: Introductionmentioning

confidence: 99%

The diagnostic value of lower glucose consumption for IDH1 mutated gliomas on FDG-PET

et al. 2021

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Background Non-invasive diagnosis of IDH1 mutation for gliomas has great clinical significance, and PET has natural advantage to detect metabolism, as IDH mutated gliomas share lower glucose consumption. Methods Clinical data of patients with gliomas and 18F-FDG PET were retrospectively reviewed. Receiver operating characteristic curve (ROC) analysis was conducted, and standard uptake value (SUV) was estimated in combination with grades or IDH1 mutation. The glucose consumption was investigated with U251 cells expressing wild-type or mutated IDH1 by glucose assay. Quantification of glucose was determined by HPLC in clinical tissues. Meanwhile, bioinformatics and western blot were applied to analyze the expression level of metabolic enzymes (e.g. HK1, PKM2, PC) in gliomas. Results Seventy-one glioma cases were enrolled, including 30 carrying IDH1 mutation. The sensitivity and specificity dependent on SUVmax (3.85) predicting IDH1 mutation reached 73.2 and 86.7%, respectively. The sensitivity and specificity of differentiating grades by SUVmax (3.1) were 92.3 and 64.4%, respectively. Glucose consumption of U251 IDH1 mutant cells (0.209 ± 0.0472 mg/ml) was obviously lower than IDH1wild-type cells (0.978 ± 0.0773 mg/ml, P = 0.0001) and astrocyte controls (0.335 ± 0.0592 mg/ml, P = 0.0451). Meanwhile, the glucose quantity in IDH1mutant glioma samples were significantly lower than those in IDH1 wild-type tissues (1.033 ± 1.19608 vs 6.361 ± 4.3909 mg/g, P = 0.0051). Silico analysis and western blot confirmed that HK1 and PKM2 in IDH1 wild-type gliomas were significantly higher than in IDH1 mutant group, while PC was significantly higher in IDH1 mutant gliomas. Conclusion SUVmax on PET can predict IDH1 mutation with adequate sensitivity and specificity, as is supported by reduced glucose consumption in IDH1 mutant gliomas.

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“…Para el estudio del estado de la IDH, fueron realizadas coloraciones de inmunohistoquímica para la mutación R132H del gen IDH1, utilizando el clon H09 para IDH1-R132H, y se hizo secuenciación genética tipo Sanger para ambos genes, IDH1 e IDH2. Para determinar la positividad de la tinción de inmunohistoquímica, se usó como punto de corte la tinción citoplasmática en más del 10% de las células tumorales [16,17]. El análisis genético se realizó en regiones específicas de los genes IDH1 e IDH2, amplificados con primers específicos por PCR.…”

Section: Metodologíaunclassified

Detección de la mutación de la enzima isocitrato deshidrogenasa en gliomas difusos grados II, III y IV

et al. 2021

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Introducción. Los gliomas son las neoplasias malignas primarias más frecuentes del sistema nervioso central, asociadas con una mortalidad y morbilidad elevadas. Las mutaciones en los genes IDH1 e IDH2 de la enzima isocitrato deshidrogenasa (IDH) son clave en la tumorogénesis, y son consideradas un factor pronóstico importante en estas neoplasias. En este estudio se buscó determinar la presencia de mutaciones de los genes IDH1 e IDH2 en pacientes con diagnóstico de glioma difuso en diferentes grados, y su correlación con la sobrevida. Metodología. Se realizó un estudio descriptivo, prospectivo y retrospectivo. La población de estudio fueron pacientes entre los 18 y 45 años con diagnóstico de glioma difuso grado II, III y IV, atendidos en el Hospital San Vicente Fundación de Medellín, entre 2012 y 2017, en quienes se realizó un análisis de mutaciones en los genes IDH1 e IDH2 por secuenciación Sanger y tinción de inmunohistoquímica. Resultados. Se incluyeron 14 pacientes con edad promedio de 37 años, 57% de sexo masculino. Glioblastoma fue la neoplasia más frecuente, diagnosticada en el 42,9% de casos. Por inmunohistoquímica, 10 de los 14 (71,4%) pacientes presentaron mutación de la enzima IDH1, en tanto que 1 de los 11 (9%) pacientes en quienes se logró la secuenciación del gen IDH2, mostró mutación. En general, el 78,6% presentó mutaciones de la enzima IDH, con promedio de sobrevida de 48 meses. Conclusión. Estos hallazgos sugieren que los gliomas son un grupo heterogéneo de tumores, con gran variabilidad genética que impacta en su pronóstico y comportamiento.

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Determining IDH-Mutational Status in Gliomas Using IDH1-R132H Antibody and Polymerase Chain Reaction

Cited by 23 publications

References 22 publications

Molecular classification of diffuse gliomas

Molecular classification of diffuse gliomas

The diagnostic value of lower glucose consumption for IDH1 mutated gliomas on FDG-PET

Detección de la mutación de la enzima isocitrato deshidrogenasa en gliomas difusos grados II, III y IV

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