Erratum to Clinical management and survival outcomes of patients with different molecular subtypes of diffuse gliomas in China(2011-2017):a multicenter retrospective study from CGGA

In the published version of Figure 21,an error appeared in Figure 2C on page 1468.In Figure 2C,the Kaplan-Meier estimation of the overall survival of patients with recurrent DG classified according to molecular subtypes was mistakenly covered by the curves of patients with primary DGs during the figure layout process,while the number statistic under the figure is correct.Figure 2C has been updated to correct this mistake.The error does not affect the conclusions of this article.We apologize for the error and for any confusion that it might have caused.

Evolution-driven crosstalk between glioblastoma and the tumor microenvironment

Glioblastoma(GBM)is a malignant adult brain tumor for which 90%of patients experience recurrence within a year after surgery1.Evolution confers treatment resistance capabilities on tumors2.The diversification of malignant and non-malignant(i.e.,stromal and immune cell)compartments in the tumor microenvironment(TME)during tumor evolution3-7 eventually results in the formation of a complex interaction network that promotes tumor progression.

Clinical management and survival outcomes of patients withdifferent molecular subtypes of diffuse gliomas in China(2011–2017):a multicenter retrospective study from CGGA

Objective:We aimed to summarize the clinicopathological characteristics and prognostic features of various molecular subtypes of diffuse gliomas(DGs)in the Chinese population.Methods:In total,1,418 patients diagnosed with DG between 2011 and 2017 were classified into 5 molecular subtypes according to the 2016 WHO classification of central nervous system tumors.The IDH mutation status was determined by immunohistochemistry and/or DNA sequencing,and 1p/19q codeletion was detected with fluorescence in situ hybridization.The median clinical follow-up time was 1,076 days.T-tests and chi-square tests were used to compare clinicopathological characteristics.Kaplan‒Meier and Cox regression methods were used to evaluate prognostic factors.Results:Our cohort included 15.5%lower-grade gliomas,IDH-mutant and 1p/19q-codeleted(LGG-IDHm-1p/19q);18.1%lowergrade gliomas,IDH-mutant(LGG-IDHm);13.1%lower-grade gliomas,IDH-wildtype(LGG-IDHwt);36.1%glioblastoma,IDHwildtype(GBM-IDHwt);and 17.2%glioblastoma,IDH-mutant(GBM-IDHm).Approximately 63.3%of the enrolled primary gliomas,and the median overall survival times for LGG-IDHm,LGG-IDHwt,GBM-IDHwt,and GBM-IDHm subtypes were 75.97,34.47,11.57,and 15.17 months,respectively.The 5-year survival rate of LGG-IDHm-1p/19q was 76.54%.We observed a significant association between high resection rate and favorable survival outcomes across all subtypes of primary tumors.We also observed a significant role of chemotherapy in prolonging overall survival for GBM-IDHwt and GBM-IDHm,and in prolonging post-relapse survival for the 2 recurrent GBM subtypes.Conclusions:By controlling for molecular subtypes,we found that resection rate and chemotherapy were 2 prognostic factors associated with survival outcomes in a Chinese cohort with DG.

Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma

Objective:O6 methylguanine-DNA methyltransferase(MGMT)promoter methylation is a biomarker widely used to predict the sensitivity of IDH-wildtype glioblastoma to temozolomide therapy.Given that the IDH status has critical effects on the survival and epigenetic features of glioblastoma,we aimed to assess the role of MGMT promoter methylation in IDH-mutant glioblastoma.Methods:This study included 187 IDH-mutant glioblastomas and used 173 IDH-wildtype glioblastomas for comparison.KaplanMeier curves and multivariate Cox regression were used to study the predictive effects.Results:Compared with IDH-wildtype glioblastomas,IDH-mutant glioblastomas showed significantly higher(P<0.0001)MGMT promoter methylation.We demonstrated that MGMT promoter methylation status,as determined by a high cutoff value(≥30%)in pyrosequencing,could be used to significantly stratify the survival of 50 IDH-mutant glioblastomas receiving temozolomide therapy(cohort A);this result was validated in another cohort of 25 IDH-mutant glioblastomas(cohort B).The median progression-free survival and median overall survival in cohort A were 9.33 and 13.76 months for unmethylated cases,and 18.37 and 41.61 months for methylated cases,and in cohort B were 6.97 and 9.10 months for unmethylated cases,and 23.40 and 26.40 months for methylated cases.In addition,we confirmed that the MGMT promoter methylation was significantly(P=0.0001)correlated with longer OS in IDH-mutant patients with GBM,independently of age,gender distribution,tumor type(primary or recurrent/secondary),and the extent of resection.Conclusions:MGMT promoter methylation has predictive value in IDH-mutant glioblastoma,but its cutoff value should be higher than that for IDH-wildtype glioblastoma.

Epidemiological characteristics and genetic alterations in adult diffuse glioma in East Asianpopulations

Understanding the racial specificities of diseases—such as adult diffuse glioma,the most common primary malignant tumor of the central nervous system—is a critical step toward precision medicine.Here,we comprehensively review studies of gliomas in East Asian populations and other ancestry groups to clarify the racial differences in terms of epidemiology and genomic characteristics.Overall,we observed a lower glioma incidence in East Asians than in Whites;notably,patients with glioblastoma had significantly younger ages of onset and longer overall survival than the Whites.Multiple genome-wide association studies of various cohorts have revealed single nucleotide polymorphisms associated with overall and subtype-specific glioma susceptibility.Notably,only 3 risk loci—5p15.33,11q23.3,and 20q13.33—were shared between patients with East Asian and White ancestry,whereas other loci predominated only in particular populations.For instance,risk loci 12p11.23,15q15-21.1,and 19p13.12 were reported in East Asians,whereas risk loci 8q24.21,1p31.3,and 1q32.1 were reported in studies in White patients.Although the somatic mutational profiles of gliomas between East Asians and non-East Asians were broadly consistent,a lower incidence of EGFR amplification in glioblastoma and a higher incidence of 1p19q-IDH-TERT triple-negative low-grade glioma were observed in East Asian cohorts.By summarizing large-scale disease surveillance,germline,and somatic genomic studies,this review reveals the unique characteristics of adult diffuse glioma among East Asians,to guide clinical management and policy design focused on patients with East Asian ancestry.

Role of the tumor microenvironment in shaping IDH-wildtype glioma plasticity,and potential therapeutic strategies

Diffuse glioma is the most common primary malignant brain tumor in adults.Currently,the prognosis of glioma remains dismal,and almost all patients with glioma experience recurrence even after comprehensive treatment including maximal surgical resection,radiotherapy,and/or chemotherapy1.Gliomas can be stratified according to their IDH mutation status.As we have previously reported2,3,the genetic characteristics,pathogenesis,and chemotherapy response are distinct between IDH-mutant and IDH-wildtype tumors.For instance,IDH-wildtype tumors are associated with poor prognosis and frequently have genomic alterations,including a gain of chromosome 7 and loss of chromosome 10.IDHmutant tumors often show findings including CpG island hypermethylation and MET alterations.

Chinese Glioma Genome Atlas(CGGA):A Comprehensive Resource with Functional Genomic Data from Chinese Glioma Patients

Gliomas are the most common and malignant intracranial tumors in adults.Recent studies have revealed the significance of functional genomics for glioma pathophysiological studies and treatments.However,access to comprehensive genomic data and analytical platforms is often limited.Here,we developed the Chinese Glioma Genome Atlas(CGGA),a user-friendly data portal for the storage and interactive exploration of cross-omics data,including nearly 2000 primary and recurrent glioma samples from Chinese cohort.Currently,open access is provided to whole-exome sequencing data(286 samples),mRNA sequencing(1018 samples)and microarray data(301 samples),DNA methylation microarray data(159 samples),and microRNA microarray data(198 samples),and to detailed clinical information(age,gender,chemoradiotherapy status,WHO grade,histological type,critical molecular pathological information,and survival data).In addition,we have developed several tools for users to analyze the mutation profiles,mRNA/microRNA expression,and DNA methylation profiles,and to perform survival and gene correlation analyses of specific glioma subtypes.This database removes the barriers for researchers,providing rapid and convenient access to high-quality functional genomic data resources for biological studies and clinical applications.CGGA is available at http://www.cgga.org.cn.

Molecular pathology and clinical implications of diffuse glioma

The prognosis for diffusely infiltrating gliomas at World Health Organization(WHO)grade 2-4 remains dismal due to their heterogeneity.The rapid development of genome-wide molecular-profiling-associated studies has greatly promoted the accuracy of glioma classification.Thus,the latest version of the WHO classification of the central nervous system tumors published in 2021 has incorporated more molecular biomarkers together with histological features for the diagnosis of gliomas.Advanced usage of molecular pathology in clinical diagnostic practice provides also new opportunities for the therapy of patients with glioma,including surgery,radiotherapy and chemotherapy,targeted therapy,immunotherapy,and more precision clinical trials.Herein,we highlight the updates in the classification of gliomas according to the latest WHO guidelines and summarize the clinically relevant molecular markers by focusing on their applications in clinical practice.We also review the advances in molecular features of gliomas,which can facilitate the development of glioma therapies,thereby discussing the challenges and future directions of molecular pathology toward precision medicine for patients with glioma.

CACA guidelines for holistic integrative management of glioma

Glioma of the brain is a kind of tumor originating from neuroglial cells.It is the most common primary intracranial tumor,accounting for~30%of all central nervous system tumors and 80% of malignant brain tumors.Glioma is characterized by high disability and recurrence rates.The disease seriously threatens the life of patients,afects their quality of life,and brings a heavy economic and psychological burden to patients,families,and society.With the progression of molecular genetic testing technology and the completion of various clinical trials,the classifcation scheme for glioma is increasingly well established.Diagnosis and treatment regimens,including traditional and new regimens,are becoming increasingly specialized and standardized.The purpose is to develop a clinical diagnosis and treatment guideline for glioma in the Chinese population suitable for Chinese doctors and the general population based on domestic and international glioma research progress.Thus,domestic practitioners in the feld can obtain current information and provide better service to patients with glioma,promoting the development of domestic clinical medicine and basic research on glioma.