Abstract 4134: Characterization of ATRX loss combined with IDH1 R132H mutation in gliomas

2028 Background: According to the 2016 WHO classification of Central Nervous System tumors, the assessment of exon 4 mutations in IDH1 or IDH2 genes is an essential step in the characterization of gliomas. The R132H mutation is the most frequent alteration in IDH1 gene, however other non-canonical IDH mutations have been identified. The aim of this study was to evaluate the prognostic role of IDH non-canonical mutations. Methods: We analyzed our institutional data warehouse for all consecutive patients (pts) with newly diagnosed, histologically proven grade II – IV IDH mutant gliomas. IDH sequencing was performed using the 454 GS-Junior next generation sequencer (NGS) (Roche Diagnostic, Mannheim, Germany). All analyses were performed on DNA from formalin fixed and paraffin embedded (FFPE) specimens. Results: The analysis included 493 pts with IDH mutations. We found 279 (56.6%) grade 2, 173 grade 3 (35.1%) gliomas, and 41 (8.3%) IDH mutant glioblastoma. Canonical IDH1 R132H mutation was found in 428 pts (86.8%). The remaining pts showed IDH2 (3.9%) or IDH 1 non-canonical mutations (mainly R132C, R132G, R132S – 9.3%). Median follow-up time was 80.5 months. Pts with non-canonical mutations showed a younger median age (32 vs 39 years, p < 0.001). Other clinical characteristics and treatments were similar across IDH groups. Median survival was 145 months (95%CI: 137.7 - 152.9) and 198.6 (95%CI 155.2– 242.1) in patients with IDH R132H and non-canonical mutations, respectively (p = 0.013). In multivariate analysis grading (p < 0.001), extent of surgery (p < 0.001), 1p19q codeletion (p = 0.003) and presence of non-canonical mutations (p = 0.022) showed a significant role for improved survival. Conclusions: Detecting non-canonical IDH1 mutations is essential for diagnosis and for prognosis in patients with gliomas. Differential enzymatic activity of non-canonical IDH1 mutations, resulting in different levels 2-hydroxyglutaratecould be the reason of improved survival.

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Faculty Opinions recommendation of Monoclonal antibody specific for IDH1 R132H mutation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1165404.628382 ◽

2009 ◽

Author(s):

David Louis

Keyword(s):

Monoclonal Antibody ◽

Idh1 R132h ◽

R132h Mutation

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IDH1 Non-Canonical Mutations and Survival in Patients with Glioma

Diagnostics ◽

10.3390/diagnostics11020342 ◽

2021 ◽

Vol 11 (2) ◽

pp. 342 ◽

Cited By ~ 1

Author(s):

Enrico Franceschi ◽

Dario De Biase ◽

Vincenzo Di Nunno ◽

Annalisa Pession ◽

Alicia Tosoni ◽

...

Keyword(s):

Idh1 Mutation ◽

Who Grade ◽

Tissue Samples ◽

1P19q Codeletion ◽

Idh1 R132h ◽

Rare Mutations ◽

Grade Ii ◽

Idh1 Mutations ◽

R132h Mutation ◽

Generation Sequencing

Background: Non-canonical mutations of the isocitrate dehydrogenase (IDH) genes have been described in about 20–25% and 5–12% of patients with WHO grade II and III gliomas, respectively. To date, the prognostic value of these rare mutations is still a topic of debate. Methods: We selected patients with WHO grade II and III gliomas and IDH1 mutations with available tissue samples for next-generation sequencing. The clinical outcomes and baseline behaviors of patients with canonical IDH1 R132H and non-canonical IDH1 mutations were compared. Results: We evaluated 433 patients harboring IDH1 mutations. Three hundred and ninety patients (90.1%) had a canonical IDH1 R132H mutation while 43 patients (9.9%) had a non-canonical IDH1 mutation. Compared to those with the IDH1 canonical mutation, patients with non-canonical mutations were younger (p < 0.001) and less frequently presented the 1p19q codeletion (p = 0.017). Multivariate analysis confirmed that the extension of surgery (p = 0.003), the presence of the 1p19q codeletion (p = 0.001), and the presence of a non-canonical mutation (p = 0.041) were variables correlated with improved overall survival. Conclusion: the presence of non-canonical IDH1 mutations could be associated with improved survival among patients with IDH1 mutated grade II–III glioma.

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A gated material as immunosensor for in-tissue detection of IDH1-R132H mutation in gliomas

Sensors and Actuators B Chemical ◽

10.1016/j.snb.2021.130406 ◽

2021 ◽

pp. 130406

Author(s):

Luis Pla ◽

Félix Sancenón ◽

M. Carmen Martínez-Bisbal ◽

Ricardo Prat-Acín ◽

Inmaculada Galeano-Senabre ◽

...

Keyword(s):

Idh1 R132h ◽

R132h Mutation

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Mechanism of IDH1-R132H mutation in T cell acute lymphoblastic leukemia mouse model via the Notch1 pathway

Tissue and Cell ◽

10.1016/j.tice.2021.101674 ◽

2021 ◽

pp. 101674

Author(s):

Yonghua Liu ◽

Bingmu Fang ◽

Xiaoning Feng ◽

Yu Jiang ◽

Yuxiao Zeng ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

Mouse Model ◽

Lymphoblastic Leukemia ◽

Idh1 R132h ◽

Cell Acute Lymphoblastic Leukemia ◽

R132h Mutation

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IMST-14. IDH1 R132H MUTATION INHIBITS ANTI-GLIOMA IMMUNE RESPONSES THROUGH POST-TRANSCRIPTIONAL DOWN-REGULATION OF STAT1 AND TYPE-1 CHEMOKINES

Neuro-Oncology ◽

10.1093/neuonc/now212.370 ◽

2016 ◽

Vol 18 (suppl_6) ◽

pp. vi88-vi88

Author(s):

Gary Kohanbash ◽

Shruti Shrivastav ◽

Brian Ahn ◽

Diego Carrera ◽

Naznin Jahan ◽

...

Keyword(s):

Immune Responses ◽

Down Regulation ◽

Idh1 R132h ◽

R132h Mutation

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Abstract LB-308: Effects of the IDH1 R132H mutation on redox status and metabolism are cell type dependent but independent from D-2-hydroxyglutarate accumulation

10.1158/1538-7445.am2016-lb-308 ◽

2016 ◽

Author(s):

Evelin Schrock ◽

Julia Biedermann ◽

Khalil Abou-El-Ardat ◽

Matthias Lehmann ◽

Marina Conde ◽

...

Keyword(s):

Redox Status ◽

Cell Type ◽

Idh1 R132h ◽

R132h Mutation

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Circulating MACC1 Transcripts in Glioblastoma Patients Predict Prognosis and Treatment Response

Cancers ◽

10.3390/cancers11060825 ◽

2019 ◽

Vol 11 (6) ◽

pp. 825 ◽

Cited By ~ 4

Author(s):

Carsten Hagemann ◽

Nikolas Neuhaus ◽

Mathias Dahlmann ◽

Almuth Kessler ◽

Dennis Kobelt ◽

...

Keyword(s):

Median Overall Survival ◽

Outcome Prediction ◽

Therapy Response ◽

Primary Brain Tumor ◽

Solid Cancer ◽

Standard Regimen ◽

Mutation Status ◽

Idh1 R132h ◽

R132h Mutation ◽

Risk Categories

Glioblastoma multiforme is the most aggressive primary brain tumor of adults, but lacks reliable and liquid biomarkers. We evaluated circulating plasma transcripts of metastasis-associated in colon cancer-1 (MACC1), a prognostic biomarker for solid cancer entities, for prediction of clinical outcome and therapy response in glioblastomas. MACC1 transcripts were significantly higher in patients compared to controls. Low MACC1 levels clustered together with other prognostically favorable markers. It was associated with patients’ prognosis in conjunction with the isocitrate dehydrogenase (IDH) mutation status: IDH1 R132H mutation and low MACC1 was most favorable (median overall survival (OS) not yet reached), IDH1 wildtype and high MACC1 was worst (median OS 8.1 months), while IDH1 wildtype and low MACC1 was intermediate (median OS 9.1 months). No patients displayed IDH1 R132H mutation and high MACC1. Patients with low MACC1 levels receiving standard therapy survived longer (median OS 22.6 months) than patients with high MACC1 levels (median OS 8.1 months). Patients not receiving the standard regimen showed the worst prognosis, independent of MACC1 levels (low: 6.8 months, high: 4.4 months). Addition of circulating MACC1 transcript levels to the existing prognostic workup may improve the accuracy of outcome prediction and help define more precise risk categories of glioblastoma patients.

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