Distinct genomic profile and specific targeted drug responses in adult cerebellar glioblastoma

Cho, Hee Jin; Zhao, Junfei; Jung, Sang Won; Ladewig, Erik; Kong, Doo Sik; Suh, Yeon Lim; Lee, Yeri; Kim, Donggeon; Ahn, Sun Hee; Bordyuh, Mykola; Kang, Hyun Ju; Jason, K.; Seo, Yun Jee; Kim, Sung Tae; Lim, Do Hoon; Dho, Yun Sik; Lee, Jung Il; Seol, Ho Jun; Choi, Jung Won; Park, Woong-Yang; Park, Shin Young; Rabadán, Raúl; Nam, Do Hyun

doi:10.1093/neuonc/noy123

Cited by 35 publications

(53 citation statements)

References 41 publications

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“…Mutations and DNA copy number changes commonly observed in cerebral malignant gliomas were less frequently encountered infratentorially. Moreover, enrichment for PDGFRA and ATRX alterations was found, whereas EGFR and TERT alterations were rare [9, 13, 21, 36]. Two previous studies on methylation profiles of cGBMs have reported assignment to the MCs diffuse midline glioma H3 K27 M mutant (DMG K27), GBM RTK I, GBM MID and IDH mutant glioma subclass astrocytoma (A IDH).…”

Section: Introductionmentioning

confidence: 99%

“…Two previous studies on methylation profiles of cGBMs have reported assignment to the MCs diffuse midline glioma H3 K27 M mutant (DMG K27), GBM RTK I, GBM MID and IDH mutant glioma subclass astrocytoma (A IDH). However, the inclusion of only 14 and 4 cGBMs in these studies is a limitation for general conclusions [9, 23]. Further, the MCs AAP and GBM MID were not represented in the reference sets of the respective clustering analyses.…”

Section: Introductionmentioning

confidence: 99%

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Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities

Reinhardt

Stichel

Schrimpf

et al. 2019

acta neuropathol commun

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In this multi-institutional study we compiled a retrospective cohort of 86 posterior fossa tumors having received the diagnosis of cerebellar glioblastoma (cGBM). All tumors were reviewed histologically and subjected to array-based methylation analysis followed by algorithm-based classification into distinct methylation classes (MCs). The single MC containing the largest proportion of 25 tumors diagnosed as cGBM was MC anaplastic astrocytoma with piloid features representing a recently-described molecular tumor entity not yet included in the WHO Classification of Tumours of the Central Nervous System (WHO classification). Twenty-nine tumors molecularly corresponded to either of 6 methylation subclasses subsumed in the MC family GBM IDH wildtype. Further we identified 6 tumors belonging to the MC diffuse midline glioma H3 K27 M mutant and 6 tumors allotted to the MC IDH mutant glioma subclass astrocytoma. Two tumors were classified as MC pilocytic astrocytoma of the posterior fossa, one as MC CNS high grade neuroepithelial tumor with BCOR alteration and one as MC control tissue, inflammatory tumor microenvironment. The methylation profiles of 16 tumors could not clearly be assigned to one distinct MC. In comparison to supratentorial localization, the MC GBM IDH wildtype subclass midline was overrepresented, whereas the MCs GBM IDH wildtype subclass mesenchymal and subclass RTK II were underrepresented in the cerebellum. Based on the integration of molecular and histological findings all tumors received an integrated diagnosis in line with the WHO classification 2016. In conclusion, cGBM does not represent a molecularly uniform tumor entity, but rather comprises different brain tumor entities with diverse prognosis and therapeutic options. Distinction of these molecular tumor classes requires molecular analysis. More than 30% of tumors diagnosed as cGBM belong to the recently described molecular entity of anaplastic astrocytoma with piloid features.Electronic supplementary materialThe online version of this article (10.1186/s40478-019-0801-8) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities

Reinhardt

Stichel

Schrimpf

et al. 2019

acta neuropathol commun

View full text Add to dashboard Cite

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“…A study showed that 61% primary gliomas occur in the four lobes of the brain, frontal (25%), temporal (20%), parietal (13%), and occipital region (3%), brainstem and cerebellum only accounts for 1.2% and 0.9%, respectively [30]. Patient characteristics, histologic features, and genomic pro les are different between supratentorial glioblastoma and cerebellar glioblastomas [31]. The most impacted function region was eloquent cortex [32].…”

Section: Discussionmentioning

confidence: 99%

Clinical Features Associated with the Efficacy of Chemotherapy in Patients with Glioblastoma (GBM): A Population-based Study

Wen

Chen

Zhu

2020

Preprint

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BackgroundGlioblastoma (GBM) is a highly malignant brain tumor with poor survival and prognosis. Randomized trials have demonstrated that chemotherapy improves survival in patients with GBM. This study aims to examine the clinical characteristics that are potentially associated with the efficacy of chemotherapy and the risk factors of GBM.MethodsA total of 25,698 patients diagnosed with GBM were identified between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER). The clinical and demographic variables between groups were examined by Student's t-test and Pearson's chi-squared test. GBM-specific survival (GBMSS) and overall survival (OS) were evaluated using the Kaplan-Meier method with the log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors.ResultsPatients who received chemotherapy had better overall survival (median OS 13 vs. 3 months, HR=1.9224, 95%CI 1.8571-1.9900, p<0.0001) and better GBMSS (median GBMSS of 12 vs. 3 months, HR=1.9379, 95%CI 1.8632-2.0156, p<0.0001) compared with patients who did not. Further subgroup analysis revealed that among patients who underwent chemotherapy, those who were younger, with the well-differentiated tumor, with a supratentorial tumor, received surgery or radiotherapy had both improved OS and GBMSS. Age, race, tumor grade, tumor location, tumor size, and treatments were identified as independent prognostic factors by multivariable analyses for patients with glioblastoma. ConclusionPatients with GBM who were younger (<65 years), with the well-differentiated tumor, underwent surgery or radiotherapy can benefit more from chemotherapeutic regimens. Age, race, tumor size, tumor location, tumor grade, surgery, radiotherapy, and chemotherapy were factors associated with the prognosis of patients with GBM.

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“…However, no incidence of cAA has been reported due to its' utmost scarcity. This is not surprising that literature dealing with malignant gliomas of the cerebellum mostly consists of cerebellar glioblastomas, including both pediatric and adult patients, and brainstem tumours involving cerebellum [5,8,11,15,17,21,32,34].…”

Section: Introductionmentioning

confidence: 99%

Cerebellar anaplastic astrocytoma in adult patients: 15 consecutive cases from a single institution and literature review

Belyaev

Усачев

Ryzhova

et al. 2020

Preprint

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Adult cerebellar anaplastic astrocytomas (cAA) are rare entities and their clinical and genetic characteristics remain to be fully described. Previously, malignant gliomas of the cerebellum were combined and reviewed together (cAA and cerebellar glioblastomas (cGB), that could have possibly affected overall results. We analyzed characteristics of 15 adult patients with cAA and compared them to a series of 45 patients with a supratentorial AA (sAA). The mean age at cAA diagnosis was 39.3 years (range 19-72). A history of neurofibromatosis type I was noted in 1 patient (6.7%). An IDH-1 mutation was identified in 6/15 cases and a methylated MGMT promoter in 5/15 cases. Patients in study and control groups were matched in age, sex and IDH-1 mutation status. Patients in a study group tended to have a more frequent multifocal presentation at diagnosis (13% vs. 4.4%) and were associated with longer overall survival (50 vs. 36.5 months), but the difference did not reach statistical significance. In both cAA and supratentorial AA groups presence of the IDH-1 mutation remains a positive predictor for the survival. The present study suggests that adult cAA constitute a group of gliomas with relatively high rate of IDH-1 mutations and prognosis similar to supratentorial AA. The present study is the first to systematically compare cAA and supratentorial AA with respect to their genetic characteristics and suggests that both groups shows a similar survival prognosis.

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Distinct genomic profile and specific targeted drug responses in adult cerebellar glioblastoma

Abstract: Our results imply that unique gliomagenesis mechanisms occur in adult cerebellum and new treatment strategies are needed to provide greater therapeutic benefits for C-GBM patients.

Cited by 35 publications

References 41 publications

Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities

Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities

Clinical Features Associated with the Efficacy of Chemotherapy in Patients with Glioblastoma (GBM): A Population-based Study

Cerebellar anaplastic astrocytoma in adult patients: 15 consecutive cases from a single institution and literature review

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