IDH1/2 gene hotspot mutations in central nervous system tumours: analysis of 922 Chinese patients

Chen, Ni; Yu, Tianpin; Gong, Jing; Nie, Ling; Chen, Xueqin; Zhang, Mengni; Xu, Miao; Tan, Jun; Su, Zhengzheng; Zhong, Jinjing; Zhou, Qiao

doi:10.1016/j.pathol.2016.07.010

Cited by 27 publications

(20 citation statements)

References 19 publications

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“…Consistent with our results, other data also show that the frequency of IDH2 mutations in Chinese patients seems to be lower than in Westerner. A study from West China Hospital only found three IDH2 mutation cases (3/207, 1.4 %) in the IDH mutation Chinese patients, for two cases of IDH2 R172K and one case of R172M mutation [13], the frequency is similar to another study of IDH2(R172K) in Chinese patients (3/203, 1.5 %) [34]. Interestingly, in other diseases which carry IDH mutations such as hematological disorders, mutation rate was also lower in Chinese patients in contrast with the findings reported by North American and European populations [35].…”

Section: Discussionmentioning

confidence: 95%

Practice of the New Integrated Molecular Diagnostics in Gliomas: Experiences and New Findings in a Single Chinese Center

Hu¹,

Wang²,

Xi³

et al. 2020

J. Cancer

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Background:The latest WHO classification of CNS tumors using the integrated phenotypic and molecular parameters (IDH, ATRX, 1p19q, TERT etc.) have reestablished the CNS tumors classification in addition to traditional histology. The establishment of glioma molecular typing can more accurately predict prognosis, better guide individualized treatment to improve survival. Methods: The expression of IDH1, ATRX, PHH3, P53 and Ki67 was detected by IHC. Molecular status of IDH1/2 and TERT were analyzed using Sanger sequencing. MGMT was explored using methylation-specific PCR. 1p/19q codeletion status was firstly detected by FISH, then further confirmed by multiplex PCR-based next generation sequencing. Results: The mutation frequency of IDH1 was 68.7% (79/115) in WHO II astrocytoma, and 82 cases (82/344, 23.8%) were "triple-negative glioma" in our cohort. Multivariate COX analysis revealed that only IDH, 1p/19q, TERT and MGMT were independent prognostic factors. Noteworthily, we found 7 cases of the new molecular phenotype presented as "IDH wildtype and 1p/19q codeletion", not mentioned in the latest WHO guideline. Conclusion: We detected the newly recommended markers in a large cohort of Chinese glioma patients. Our data demonstrated a relatively lower frequency of IDH mutations and a higher prevalence of triple-negative glioma in Chinese compared with American and European, indicating ethnic and geographical difference in some markers. In addition, the new molecular phenotype "IDH wildtype and 1p/19q codeletion" glioma deserved special focus. These findings suggest that further stratification of infiltrating gliomas is needed for different treatment strategy and precision medicine.

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Section: Discussionmentioning

confidence: 95%

Practice of the New Integrated Molecular Diagnostics in Gliomas: Experiences and New Findings in a Single Chinese Center

Hu¹,

Wang²,

Xi³

et al. 2020

J. Cancer

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“…It was widely acknowledged that prognosis is poor in midline glioma than non-midline tumor [ 10 ]. Regarding to hemispheric glioma, patient with tumor located in frontal lobe tends to be younger, IDH1 mutation and longer survival time [ 15 ]. This conclusion is accordance with our result.…”

Section: Discussionmentioning

confidence: 99%

Anatomic mapping of molecular subtypes in diffuse glioma

Tang

Lian

et al. 2017

BMC Neurol

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BackgroundTumor location served as an important prognostic factor in glioma patients was considered to postulate molecular features according to cell origin theory. However, anatomic distribution of unique molecular subtypes was not widely investigated. The relationship between molecular phenotype and histological subgroup were also vague based on tumor location. Our group focuses on the study of glioma anatomic location of distinctive molecular subgroups and histology subtypes, and explores the possibility of their consistency based on clinical background.MethodsWe retrospectively reviewed 143 cases with both molecular information (IDH1/TERT/1p19q) and MRI images diagnosed as cerebral diffuse gliomas. The anatomic distribution was analyzed between distinctive molecular subgroups and its relationship with histological subtypes. The influence of tumor location, molecular stratification and histology diagnosis on survival outcome was investigated as well.ResultsAnatomic locations of cerebral diffuse glioma indicate varied clinical outcome. Based on that, it can be stratified into five principal molecular subgroups according to IDH1/TERT/1p19q status. Triple-positive (IDH1 and TERT mutation with 1p19q codeletion) glioma tended to be oligodendroglioma present with much better clinical outcome compared to TERT mutation only group who is glioblastoma inclined (median overall survival 39 months VS 18 months). Five molecular subgroups were demonstrated with distinctive locational distribution. This kind of anatomic feature is consistent with its corresponding histological subtypes.DiscussionEach molecular subgroup in glioma has unique anatomic location which indicates distinctive clinical outcome. Molecular diagnosis can be served as perfect complementary tool for the precise diagnosis. Integration of histomolecular diagnosis will be much more helpful in routine clinical practice in the future.

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“…The 2016, the World Health Organizations’ Classification of Tumors of the Central Nervous System redrew the family trees of diffuse gliomas, classifying according to their molecular characteristics, one of which is isocitrate dehydrogenase (IDH) status . The IDH profile of glioblastoma (GBM) and other high‐grade glial tumors has been well established in large case studies . The IDH profile of the more rare gliosarcoma (GSC), a grade IV lesion comprising approximately 2% of all GBM, has been studied in multiple nonimaging series …”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] The IDH profile of glioblastoma (GBM) and other high-grade glial tumors has been well established in large case studies. 4 The IDH profile of the more rare gliosarcoma (GSC), a grade IV lesion comprising approximately 2% of all GBM, has been studied in multiple nonimaging series. [5][6][7] In the largest known histologic study of 36 patients, GSC was found to be universally IDH wild-type, suggesting that it is a derivative, or genetic variant of primary GBM.…”

Section: Introductionmentioning

confidence: 99%

Gliosarcoma: Neuroimaging and Immunohistochemical Findings

Peckham

Osborn

Palmer

et al. 2018

Journal of Neuroimaging

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BACKGROUND AND PURPOSE Gliosarcoma (GSC) is an intra‐axial lesion which often abuts a dural margin and is composed of glial and mesenchymal elements. This lesion is considered a variant of isocitrate dehydrogenase (IDH)‐wild type glioblastoma (GBM). The purpose of this study is to evaluate the imaging and molecular features of GSC in a large patient cohort. METHODS Pathology‐proved GSC cases were collected from our quaternary care center spanning the last 16 years and IDH status was documented. Older GSC cases without prior immunohistochemical testing underwent tissue block staining to obtain IDH status. When available, p53, phosphate and tensin (PTEN), MIB‐1, EGFR amplification, and MGMT methylation were recorded and imaging findings tabulated. Logistic regression analyses were performed to determine correlation of molecular markers and imaging characteristics. RESULTS A total of 25 cases were identified (21 de novo, 4 post‐treatment). All lesions contacted a dural, pial, or ependymal surface and were negative for an IDH R132H mutation, including postradiation GSC. In total, 16 of 16 cases showed nonamplification of EGFR/CEP7, 2 of 16 demonstrated MGMT methylation, and multiple lesions demonstrated p53 and PTEN mutations. Imaging features included areas of nodular thickening in necrotic lesions which appeared to abut the site of dural contact. There was no significant correlation of molecular markers with imaging characteristics. CONCLUSION GSC was IDH(–) in all cases, supporting the current understanding of this lesion being a wild‐type GBM variant. Additional molecular markers demonstrated no significant correlation with imaging findings in this cohort.

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IDH1/2 gene hotspot mutations in central nervous system tumours: analysis of 922 Chinese patients

Cited by 27 publications

References 19 publications

Practice of the New Integrated Molecular Diagnostics in Gliomas: Experiences and New Findings in a Single Chinese Center

Practice of the New Integrated Molecular Diagnostics in Gliomas: Experiences and New Findings in a Single Chinese Center

Anatomic mapping of molecular subtypes in diffuse glioma

Gliosarcoma: Neuroimaging and Immunohistochemical Findings

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