Detection of IDH1 Mutation in cfDNA and Tissue of Adult Diffuse Glioma with Allele-Specific qPCR

Background: The World Health Organization (WHO) classification of central nervous system (CNS) tumors necessitates testing of isocitrate dehydrogenase (IDH) 1/2 gene mutation in patients with adult-type diffuse glioma (ADG) for better disease management. In clinical practice, the testing of IDH1 is primarily achieved using immunohistochemistry (IHC) specific to IDH1-R132, which carries a sensitivity of 80% and specificity of 100%. However, in some cases, non-specific background staining or regional heterogeneity in the protein expression of IDH1 may necessitate confirmatory genetic analysis. Robust and reliable assays are needed for IDH1/2 mutation testing. The aim of the current study was to detect IDH1 mutation in cfDNA and tissue of adult-type diffuse glioma with allele-specific qPCR. Materials and Methods: In the current study, IDH1-R132H mutation was analyzed in tumor tissue with paired cell-free DNA (cfDNA) in patients with ADG (n = 45) using IHC and competitive allele-specific Taqman PCR (CAST-PCR). Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue and matched serum for cfDNA using commercially available kits. CAST-PCR with IHC for the detection of IDH1-R132H mutation was also compared. Results: The IDH1-R132H mutation was detected in 46.67% (21/45) cases and 57.78% (26/45) cases using IHC and allele-specific CAST-PCR. In cfDNA of matched IDH1-mutant FFPE tissue DNA, IDH1-R132H mutation was detected in 11.54% (3/26) using CAST-PCR. The concordance rate for IDH1-R132Hmutation between IHC and CAST-PCR was 80.77% (21/26). Conclusion: The CAST-PCR assay is more precise and sensitive for  IDH1-R132Hdetection than traditional IHC, and IDH1-R132H mutation detection using cfDNA may add to the current methods of glioma genomic characterization.     

Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing

Isocitrate dehydrogenase 1 (IDH1) mutations have recently been identified as early and frequent genetic alterations in astrocytomas, oligodendrogliomas, and oligoastrocytomas, as well as secondary glioblastomas, whereas primary glioblastomas very rarely contain IDH1 mutations. Furthermore, a specific monoclonal antibody, IMab-1, which recognizes IDH1-R132H—the most frequent IDH1 mutation—has been generated. IMab-1 has been reported to react with the IDH1-R132H protein, but not the wild-type IDH1 or the other IDH1 mutant proteins in Western-blot analysis. However, the importance of immunohistochemistry using IMab-1 has not yet been elucidated. In this study, we compared the findings from IMab-1 immunohistochemistry and direct DNA sequencing using 49 glioma samples. IMab-1 detected 12 out of 49 cases; however, only nine cases were found to be IDH1-R132H by direct DNA sequencing because of a small population of IDH1-R132H mutation-possessing tumor cells, indicating that IMab-1 immunohistochemistry is useful for detecting IDH1-R132H. We conducted immunohistochemical detection in 52 cases of grade III astrocytomas. The median time to progression (TTP) was significantly longer in the cases with the IDH1 mutation (86.7 months) compared to the cases without the IDH1 mutation (wild type, 10.4 months) (p < 0.01). In conclusion, the anti-IDH1-R132H-specific monoclonal antibody IMab-1 is very useful for detecting IDH1-R132H in immunohistochemistry, and predicting the time to progression in grade III anaplastic astrocytomas. Therefore, IMab-1 is likely to be useful for the diagnosis of mutation-bearing gliomas and for determining the treatment strategy of grade III gliomas.     

Characterizing invading glioma cells based on IDH1-R132H and Ki-67 immunofluorescence

Glioma, the most common primary brain tumor, is characterized by proliferative-invasive growth. However, the detailed biological characteristics of invading glioma cells remain to be elucidated. A monoclonal antibody (clone HMab-1) that specifically and sensitively recognizes the isocitrate dehydrogenase-1 (IDH1) protein carrying the R132H mutation can identify invading glioma cells by immunostaining. To investigate the degree of invasion in gliomas of distinct grades and the proliferative capacity of the invading cells, immunofluorescent staining was conducted using antibodies against IDH1-R132H and Ki-67 on 11 surgical and autopsy specimens of the tumor core and the invading area. Higher numbers of IDH1-R132H-positive cells in the invading area correlated with a higher tumor grade. Double staining for IDH1-R132H and Ki-67 demonstrated that most invading cells that expressed IDH1-R132H were not stained by the Ki-67 antibody, and the ratio of Ki-67-positive cells among IDH1-R132H-positive cells was significantly lower in the invasion area than in the tumor core in all grades of glioma. These data suggest that higher grade gliomas have a greater invasive potential and that invading cells possess low proliferative capacity.     

Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing

Background

Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Most authors have used DNA-based methods to assess IDH1 status. Preliminary studies comparing imunohistochemistry (IHC) with IDH1-R132H mutation-specific antibodies have shown concordance with DNA sequencing and no cross-reactivity with wild-type IDH1 or other mutant proteins. The present study compares results of IHC with DNA sequencing in diffuse gliomas.

Materials and methods

Fifty diffuse gliomas with frozen tissue samples for DNA sequencing and adequate tissue in paraffin blocks for IHC using IDH1-R132H specific antibody were assessed for IDH1 mutations.

Results

Concordance of findings between IHC and DNA sequencing was noted in 88% (44/50) cases. All 6 cases with discrepancy were immunopositive with DIA-H09 antibody. While in 3 of these 6 cases, DNA sequencing failed to reveal any mutations, R132L (arginine replaced by leucine) mutation was found in the rest 3 cases. Interestingly, of the immunopositive cases, 46.6% (14/30) showed immunostaining in only a fraction of tumor cells.

Conclusions

IHC is an easy and quick method of detecting IDH1-R132H mutations, but there may be some discrepancies between IHC and DNA sequencing. Although there were no false-negative cases, cross-reactivity with IDH1-R132L was seen in 3, a finding not reported thus far. Because of more universal availability of IHC over genetic testing, cross-reactivity and staining heterogeneity may have bearing over its use in detecting IDH1-R132H mutation in gliomas.     

Immunohistochemical detection of IDH1 mutation, p53, and internexin as prognostic factors of glial tumors

Isocitrate dehydrogenase 1 (IDH1) mutations, which are early and frequent genetic alterations in astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary glioblastomas, are specific to arginine 132 (R132). Recently, we established monoclonal antibodies (mAbs) against IDH1 mutations: anti-IDH1-R132H and anti-IDH1-R132S. However, the importance of immunohistochemistry using the combination of those mAbs has not been elucidated. For this study, 164 cases of glioma were evaluated immunohistochemically for IDH1 mutations (R132H and R132S) using anti-IDH1 mAbs (HMab-1 and SMab-1). IDH1 mutation was detected, respectively, in 9.7%, 63.6%, 51.7%, and 77.8% of primary grade IV, secondary grade IV, grade III, and grade II gliomas. For each grade of glioma, prognostic factors for progression-free survival and overall survival were evaluated using clinical and pathological parameters in addition to IDH1 immunohistochemistry. IDH1 mutation, p53 overexpression, and internexin expression, as evaluated using immunohistochemistry with clinical parameters such as degree of surgical removal and preoperative Karnofsky Performance Status (KPS), might be of greater prognostic significance than histological grading alone in grade III as well as IDH1 mutation in grade IV gliomas.     

Combining two biomarkers, IDH1/2 mutations and 1p/19q codeletion, to stratify anaplastic oligodendroglioma in three groups: a single-center experience

IDH1/2 mutations and 1p/19q codeletion occur frequently in anaplastic gliomas and are prognostic factors. We combined these two biomarkers to stratify patients treated for anaplastic oligodendroglioma (AO). 43 consecutive WHO AO were selected. We combined immunohistochemistry (IHC) with the monoclonal antibody mIDH1R132H and DNA sequencing of IDH1 and IDH2 genes. Fluorescence in situ hybridization was carried out to evaluate 1p/19q codeletion. These biomarkers were correlated with progression-free survival (PFS) and overall survival (OS). IDH1/IDH2 mutations occurred in 23/43 (54 %) patients: 20/43 IDH1-R132H mutation in IHC, 2/43 IDH1-R132G mutation and 1/43 IDH2-R172K mutation identified by DNA sequencing. 1p/19q codeletion was detected for 23/43 patients. With median follow-up of 19 months (range 1.4–128), median PFS and OS were 22 and 35 months respectively. IDH1/IDH2 mutations were strongly associated with improved PFS and OS: 5-year PFS was 86 versus 6 % and 5-year OS was 91 versus 9 % for patients with IDH1/IDH2 mutations versus wild-type IDH respectively. In multivariate analyses, IDH1/IDH2 mutations and 1p/19q loss were independent prognostic factors. Three groups with distinct prognostic features were identified: patients with IDH1/2 mutations and 1p/19q loss (median PFS, median OS not reached), patients with IDH1/2 mutations or 1p/19q loss (median PFS: 22 months, median OS: 30 months), and patients without IDH1/2 mutations nor 1p/19q loss with a bad prognosis (median PFS: 8.6 months, median OS: 9.9 months). Combining two biomarkers, IDH1/2 and 1p/19q codeletion, makes it possible to stratify AO in three groups with very distinct prognostic features.     

Prognostic stratification of gliomatosis cerebri by IDH1R132H and INA expression

Gliomatosis cerebri (GC) constitutes a heterogeneous group of conditions involving diffuse neoplastic glial cell infiltration of the brain. Management is difficult and an obvious challenge is to identify prognostic factors. Alpha-internexin (INA) expression, which is closely related to the 1p19q codeletion, is a strong prognostic marker in oligodendroglial tumors. Similarly, the R132H isocitrate dehydrogenase 1 IDH1 mutation, which can now be detected by use of a specific antibody, predicts better outcome in gliomas. In a retrospective series of 40 GC treated with up-front chemotherapy, we analyzed IDH1(R132H) mutant protein and INA immunohistochemical expression and correlated it with outcome; 17/40 GC expressed IDH1(R132H) and 10/40 GC expressed INA. IDH1(R132H) staining was strongly related to progression-free survival (42.3 vs. 15.5 months for positive IDH1(R132H) vs. negative tumors; P < 0.0001) and overall survival (73.9 vs. 23.6 months; P < 0.0001). This effect was independent of grade, histologic subtype, and INA expression (P < 0.001). Combined expression of IDH1(R132H) and INA was strongly associated with response to chemotherapy (100% vs. 36%; P = 0.003). These data strongly suggest that INA and IDH1(R132H) mutant protein immunohistochemical analysis is of a great prognostic value in biopsied GC.     

The impact of concurrent temozolomide with adjuvant radiation and IDH mutation status among patients with anaplastic astrocytoma

This study assesses the controversial role of temozolomide (TMZ) concurrent with adjuvant radiation (RT) in patients with anaplastic astrocytoma (AA). The impact of isocitrate dehydrogenase (IDH) status on therapy and outcomes is also examined. All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant RT were identified retrospectively for clinical data extraction. IDH status was determined by IDH1-R132H immunostain and sequencing for other mutations in IDH1/IDH2. Cumulative survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit for univariable/multivariable analyses. 136 patients had received concurrent TMZ while 29 had not. Of these, IDH status was determined on 114 and 27 patients, respectively. On univariable analysis, improved five-year survival was independently associated with concurrent TMZ (46.2 vs. 29.3 %, p = 0.02) and IDH mutation (78.9 vs. 22.0 %, p < 0.001). IDH mutation was additionally associated with a greater likelihood of extensive resection possibly secondary to a more favorable tumor location. Gross total/subtotal resections also led to improved survival when compared to biopsy alone on univariable analysis. On multivariable analysis, the association with five-year survival persisted for both concurrent TMZ and IDH mutation, but not with extent of surgery. Both IDH mutation and concurrent TMZ are associated with improved five-year survival in patients with AA who are receiving adjuvant RT. Secondarily, the association between five-year survival and extent of resection is lost on multivariable analysis. This suggests a possible association between IDH mutation, tumor location and consequent resectability.     

Expression of CD 133 in Invasive Ductal Carcinoma of Breast

Background: CD133 is a commonly used cancer stem cell (CSC) marker in breast cancer. However, the association between CD133 expression, with clinicopathological features and prognosis in breast cancer, is poorly understood in the Indian subcontinent. This study was designed to explore the expression of CD 133 in breast carcinoma and to know its association  between CD133 and clinicopathological characteristics. Methods: A total of fifty seven cases were included in the study. All the clinicopathological parameters were collected from Department of Pathology archives. Slides, blocks, clinical information, tumor size and axillary lymph node status were obtained from medical records and the pathology reports. Immunohistochemistry was done using CD 133 antibodies. Both Cytoplasmic and membranous staining was taken a positive. Scoring was done based on percentage of positive cells and intensity of staining. MS Excel, SPSS version 22 (IBM SPSS Statistics, Somers NY, USA) was used to analyze data.p value < 0.05 was considered as statistically significant. Results: Statistically significant association between the CD 133 expression and nodal metastasis, tumor stage and Nottingham prognostic index was analysed. There was no statistical correlation between CD 133 expression age, tumor grade and tumor size. The disease free survival showed the mean disease free survival of CD 133 positivity cases was 16months. And the patients who were negative for CD 133 expression had mean survival of 30 months. By the Kaplan Mayer graph it was evident that the more the CD 133 expression the lesser was the disease free survival of the patients. Conclusion: CD 133 expression was seen in 77.08% cases and was associated with tumor stage, lymph node metastasis, poor Nottingham prognostic index and  worse disease free survival. An increasing trend of association was seen between CD 133 expression and Age, Tumor Size and Tumor grade.     

Correlation between the prognostic value and the expression of the stem cell marker CD133 and isocitrate dehydrogenase1 in glioblastomas

Cancer stem cells are thought to be responsible for tumor recurrence and resistance in glioblastomas. An isocitrate dehydrogenase1 (IDH1) mutation, affecting codon132 of the isocitrate dehydrogenase1 gene, has prognostic significance in glioblastomas. We investigated whether stem cell marker expression [CD133, CD34, and vascular endothelial growth factor (VEGF)] and IDH1 mutation correlate with clinical factors and prognosis in glioblastoma. CD133, CD34, and VEGF expression was evaluated by immunohistochemistry in 67 cases of glioblastoma identified between 2005 and 2012. IDH1 mutation was assessed by immunohistochemistry, peptide-nucleic-acid mediated PCR clamping, and direct gene sequencing. Diffuse CD133 expression was detected in 12 (17.9 %) cases and was associated with poor overall survival (OS) (P = 0.010) and progression-free survival (P = 0.017). CD34 and VEGF expression were not associated with prognosis in these samples. IDH1 mutation was detected in ten (14.9 %) cases. Eight were clinically secondary tumors and two were primary tumors (P < 0.001); the mean age of the secondary tumor patients was significantly younger (P = 0.001, 41.20 vs. 59.14). IDH1-positive patients had longer OS than IDH1-negative patients (25.78 vs. 22.95 months), but this difference was not significant. In addition, IDH1 and CD34 expression showed a negative correlation (P = 0.024). Multivariate analysis showed that age, extent of surgery, and diffuse CD133 expression correlated with OS. CD133 may be a survival marker for glioblastoma. Further characterization of CD133, IDH1, and vascular markers in glioblastoma may help identify new therapeutic targets.     

全自动免疫组化法与一代测序技术在检测人脑胶质瘤异柠檬酸脱氢酶1突变中的应用价值比较

目的:通过比较全自动免疫组化法与一代测序技术在检测人脑胶质瘤异柠檬酸脱氢酶1(isocitrate dehydrogenase 1,IDH1)基因突变中的优点和缺点,为临床检测脑胶质瘤IDH1基因突变提供有效的方案.方法:收集99例石蜡包埋的临床脑胶质瘤手术标本,采用全自动免疫组化染色机进行IDH1-R132H免疫组化...     

野生型IDH1和突变型IDH1过表达对肺癌细胞增殖的作用研究

目的:检测野生型IDH1（IDH1WT）和R132H突变型IDH1(IDH1R132H)过表达对肺癌细胞增殖和克隆形成能力的影响。方法:构建IDH1WT和IDH1R132H过表达载体:pcDNA3.1/IDH1WT和pcDNA3.1/IDH1R132H,转染H446细胞筛选过表达的细胞模型H446-IDH1WT和H446-IDH1R132H。利用全息无标记细胞成像分析系统和CCK8实验检测H446-IDH1WT和H446-IDH1R132H细胞的增殖能力,克隆形成实验检测IDH1WT和IDH1R132H过表达对H446细胞克隆形成能力的影响。利用流式细胞术检测IDH1WT和IDH1R132H过表达对H446细胞周期的影响。结果:IDH1WT和IDH1R132H过表达均可促进H446细胞的增殖和克隆形成能力,且IDH1R132H过表达的促进作用更强。IDH1WT和IDH1R132H过表达可引起H446细胞周期G2/M期阻滞。结论:IDH1R132H过表达对肺癌H446细胞增殖和克隆形成具有较强的促进作用。     

Comparison of immunohistochemistry, DNA sequencing and allele-specific PCR for the detection of IDH1 mutations in gliomas

Previous studies have identified mutations of the isocitrate dehydrogenase 1 (IDH1) gene in more than 70% of World Health Organization (WHO) grade II and III gliomas. The most frequent mutation leads to a specific amino acid change from arginine to histidine at codon 132 (c.395G>A, p.R132H). IDH1 mutated tumors have a better prognosis than IDH1 non-mutated tumors. The aim of our study was to evaluate and compare the methods of mIDH1 R132H immunohistochemistry, allele-specific PCR and DNA sequencing for determination of IDH1 status. We performed a retrospective study of 91 patients with WHO grade II (n=43) and III (n=48) oligodendrogliomas. A fragment of exon 4 spanning the sequence encoding the catalytic domain of IDH1, including codon 132, was amplified and sequenced using standard conditions. Allele-specific amplification was performed using two forward primers with variations in their 3' nucleotides such that each was specific for the wild-type or the mutated variant, and one reverse primer. Immunohistochemistry was performed with mouse monoclonal mIDH1 R132H. DNA was extracted from FFPE sections following macrodissection. IDH1 mutations were found in 55/90 patients (61.1%) by direct sequencing. R132H mutations were found in 47/55 patients (85.4%). The results of the allele-specific PCR positively correlated with those from DNA sequencing. Other mutations (p.R132C, p.R132S and pR132G) were found by DNA sequencing in 3, 3 and 2 tumors, respectively (8/55 patients, 14.6%). mIDH1 R132H immunostaining was found in the 47 patients presenting the R132H mutation (sensitivity 47/47, 100% for this mutation). None of the tumors presenting a wild-type IDH1 gene were stained (specificity 35/35, 100%). Our results demonstrate that immunohistochemistry using the mIDH1 R132H antibody and allele-specific amplification are highly sensitive techniques to detect the most frequent mutation of the IDH1 gene.     

Association of The IDH1 C.395G>A (R132H) Mutation with Histological Type in Malay Brain Tumors

Background: Brain tumors, constituting one of the most deadly forms of cancer worldwide, result from the accumulation of multiple genetic and epigenetic alterations in genes and signaling pathways. Isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutations are frequently identified in primary brain tumors and acute myeloid leukemia. Studies on IDH1 gene mutations have been extensively performed in various populations worldwide but not in Malaysia. This work was conducted to study the prevalence of IDH1 c.395G>A (R132H) hotspot mutations in a group of Malaysian patients with brain tumors in order to gain local data for the IDH1 mutation profile in our population. Methods: Mutation analysis of c.395G>A (R132H) of IDH1 was performed in 40 brain tumor specimens by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and then verified by direct sequencing. Associations between the IDH1 c.395G>A (R132H) mutation and clinicopathologic characteristics were also analyzed. Results: The IDH1 c.395G>A (R132H) mutation was detected in 14/40 patients (35%). A significant association was found with histological tumor types, but not with age, gender and race. Conclusions: IDH1 is frequently mutated and associated with histological subtypes in Malay brain tumors.     

人异柠檬酸脱氢酶1（IDH1）R132 H突变型脑胶质瘤细胞的原代培养及鉴定

目的：建立简单、方便、高效的异柠檬酸脱氢酶1（IDH1）突变型胶质瘤原代细胞体外培养方法,为研究IDH1突变型脑胶质瘤提供细胞模型。方法：样本组织取自低级别脑胶质瘤手术患者,采用组织块法行原代细胞培养,倒置显微镜下观察细胞形态特点;瘤组织应用苏木精－伊红染色法（HE ）和免疫组织化学染色确定胶质瘤病理类型以及级别;原代细胞提取基因组行碱基序列测序以鉴定IDH1突变类型;采用MTT法绘制生长曲线,检测IDH1突变型细胞的体外增殖特性。结果：成功建立WHOⅡ级IDH1 R132H突变型人脑星形胶质细胞瘤细胞株,并可传代。结论：应用合适的方法以及培养液,可以培养出IDH1 R132H突变型人脑胶质瘤原代细胞。     

Epigenetic suppression of EGFR signaling in G-CIMP+ glioblastomas

The intrinsic signaling cascades and cell states associated with the Glioma CpG Island Methylator Phenotype (G-CIMP) remain poorly understood. Using published mRNA signatures associated with EGFR activation, we demonstrate that G-CIMP+ tumors harbor decreased EGFR signaling using three independent datasets, including the Chinese Glioma Genome Atlas(CGGA; n=155), the REMBRANDT dataset (n=288), and The Cancer Genome Atlas (TCGA; n=406). Additionally, an independent collection of 25 fresh-frozen glioblastomas confirmed lowered pERK levels in G-CIMP+ specimens (p<0.001), indicating suppressed EGFR signaling. Analysis of TCGA glioblastomas revealed that G-CIMP+ glioblastomas harbored lowered mRNA levels for EGFR and H-Ras. Induction of G-CIMP+ state by exogenous expression of a mutated isocitrate dehydrogenase 1, IDH1-R132H, suppressed EGFR and H-Ras protein expression as well as pERK accumulation in independent glioblastoma models. These suppressions were associated with increased deposition of the repressive histone markers, H3K9me3 and H3K27me3, in the EGFR and H-Ras promoter regions. The IDH1-R132H expression-induced pERK suppression can be reversed by exogenous expression of H-RasG12V. Finally, the G-CIMP+ Ink4a-Arf^−/− EGFRvIII glioblastoma line was more resistant to the EGFR inhibitor, Gefitinib, relative to its isogenic G-CIMP- counterpart. These results suggest that G-CIMP epigenetically regulates EGFR signaling and serves as a predictive biomarker for EGFR inhibitors in glioblastoma patients.     

Interlaboratory comparison of IDH mutation detection

Isocitrate dehydrogenase (IDH) mutational testing is becoming increasingly important. For this, robust and reliable assays are needed. We tested the variation of results between six laboratories of testing for IDH mutations. Each laboratory received five unstained slides from 31 formalin-fixed paraffin-embedded (FFPE) glioma samples, and followed its own standard IDH diagnostic routine. All laboratories used immunohistochemistry (IHC) with an antibody against the most frequent IDH1 mutation (R132H) as a first step. Three laboratories then sequenced only IHC negative cases while the others sequenced all cases. Based on the overall analysis, 13 samples from 11 tumors had an R132H mutation and one tumor showed an R132G mutation. Results of IHC for IDH1 R132H mutations in all six laboratories were completely in agreement, and identified all R132H mutations. Upon sequencing the results of two laboratories deviated from those of the others. After a review of the entire diagnostic process, on repeat (blinded) testing one laboratory was completely in agreement with the overall result. A change in technique did only partially improve the results in the other laboratory. IHC for the IDH1 R132H mutation is very reliable and consistent across laboratories. IDH sequencing procedures yielded inconsistent results in 2 out of 6 laboratories. Quality assurance is pivotal before IDH testing is made part of clinical management of patients.     

C-terminally truncated form of αB-crystallin is associated with IDH1 R132H mutation in anaplastic astrocytoma

Malignant gliomas are the most common human primary brain tumors. Point mutation of amino acid arginine 132 to histidine (R132H) in the IDH1 protein leads to an enzymatic gain-of-function and is thought to promote gliomagenesis. Little is known about the downstream effects of the IDH1 mutation on protein expression and how and whether changes in protein expression are involved in tumor formation or propagation. In the current study, we used 2D DIGE (difference gel electrophoresis) and mass spectrometry to analyze differences in protein expression between IDH1^R132H mutant and wild type anaplastic (grade III) astrocytoma from human brain cancer tissues. We show that expression levels of many proteins are altered in IDH1^R132H mutant anaplastic astrocytoma. Some of the most over-expressed proteins in the mutants include several forms of αB-crystallin, a small heat-shock and anti-apoptotic protein. αB-crystallin proteins are elevated up to 22-fold in IDH1^R132H mutant tumors, and αB-crystallin expression appears to be controlled at the post-translational level. We identified the most abundant form of αB-crystallin as a low molecular weight species that is C-terminally truncated. We also found that overexpression of αB-crystallin can be induced by transfecting U251 human glioblastoma cell lines with the IDH1^R132H mutation. In conclusion, the association of a C-terminally truncated form of αB-crystallin protein with the IDH1^R132H mutation is a novel finding that could impact apoptosis and stress response in IDH1 mutant glioma.