The integrated genomic and epigenomic landscape of brainstem glioma

Chen, Lee H.; Pan, Changcun; Diplas, Bill H.; Xu, Changwu; Hansen, Landon J.; Wu, Yadong; Chen, Xin; Geng, Yibo; Sun, Tao; Sun, Yu; Zhang, Peng; Wu, Zhen; Zhang, Junting; Li, Deling; Zhang, Yang; Wu, Wenhao; Wang, Yu; Li, Guangyu; Yang, Jie; Wang, Xiaoyue; Xu, Chen; Wang, Sizhen; Waitkus, Matthew S.; He, Yiping; McLendon, Roger E.; Ashley, David M.; Yan, Hai; Zhang, Liwei

doi:10.1038/s41467-020-16682-y

Cited by 58 publications

(72 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Diffuse intrinsic pontine glioma has been reported to account for~75% of brain stem tumors in children (2). Because of poor survival, brainstem glioma has been a main research focus for decades (4).…”

Section: Introductionmentioning

confidence: 99%

Epidemiology and Survival of Patients With Brainstem Gliomas: A Population-Based Study Using the SEER Database

et al. 2021

View full text Add to dashboard Cite

BackgroundBrainstem glioma is a primary glial tumor that arises from the midbrain, pons, and medulla. The objective of this study was to determine the population-based epidemiology, incidence, and outcomes of brainstem gliomas.MethodsThe data pertaining to patients with brainstem gliomas diagnosed between 2004 and 2016 were extracted from the SEER database. Descriptive analyses were conducted to evaluate the distribution and tumor-related characteristics of patients with brainstem gliomas. The possible prognostic indicators were analyzed by Kaplan-Meier curves and a Cox proportional hazards model.ResultsThe age-adjusted incidence rate was 0.311 cases per 100,000 person-years between 2004 and 2016. A total of 3387 cases of brainstem gliomas were included in our study. Most of the patients were white and diagnosed at 5-9 years of age. The most common diagnosis confirmed by histological review was ependymoma/anaplastic ependymoma. The median survival time was 24 months. Patients with tumors less than 3 cm in size had a better prognosis. Surgery was effective at improving overall survival. There was no evidence that radiotherapy and chemotherapy improved overall survival.ConclusionBrainstem gliomas can be diagnosed at any age. Ependymoma/anaplastic ependymoma is the most common pathological diagnosis. The prognosis is poor, and timely diagnosis and surgery are effective at improving the prognosis. We suggest that more attention should be given to the treatment of patients with brainstem gliomas.

show abstract

Section: Introductionmentioning

confidence: 99%

Epidemiology and Survival of Patients With Brainstem Gliomas: A Population-Based Study Using the SEER Database

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Molecular analyses usually found mutually exclusive distribution of H3 K27M with the characteristic IDH mutations. In addition to H3 K27M, ATRX, TP53, NF1, FGFR1, PDGFRA, PTPN11, and BRAF alterations have been found in various pediatric and adult midline glioma subtypes, while 1p/19q co-deletion were seldom reported (8,12,14,18,19). Many of these frequently observed genes are key members of PI3K/mTOR and RAS-MAPK pathways that could potentially provide novel therapeutic options for these otherwise devastating diseases (20)(21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Genomic Profiling Identified Novel Prognostic Biomarkers in Chinese Midline Glioma Patients

Shan

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

BackgroundMolecular characteristics are essential for the classification and grading of gliomas. However, diagnostic classification of midline glioma is still debatable and substantial molecular and clinical heterogeneity within each subgroup suggested that they should be further stratified. Here, we studied the mutation landscape of Chinese midline glioma patients in hope to provide new insights for glioma prognosis and treatment.MethodsTissue samples from 112 midline glioma patients underwent next-generation sequencing targeting 425 cancer-relevant genes. Gene mutations and copy number variations were investigated for their somatic interactions and prognostic effect using overall survival data. Pathway-based survival analysis was performed for ten canonical oncogenic pathways.ResultsWe identified several currently established diagnostic and prognostic biomarkers of glioma, including TP53 (33%), EGFR (26%), TERT (24%), PTEN (21%), PIK3CA (14%), ATRX (14%), BRAF (13%), and IDH1/2 (6%). Among all genetic aberrations with more than 5% occurrence rate, six mutations and three copy number gains were greatly associated with poor overall survival (univariate, P < 0.1). Of these, TERT mutations (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.37–6.61; P = 0.01) and PIK3CA mutations (HR, 2.04; 95% CI, 1.08–3.84; P = 0.02) remained significant in multivariate analyses. Additionally, we have also identified a novel MCL1 amplification (found in 31% patients) as a potential independent biomarker for glioma (multivariate HR, 2.78; 95% CI, 1.53–5.08; P < 0.001), which was seldom reported in public databases. Pathway analyses revealed significantly worse prognosis with abnormal PI3K (HR, 1.81; 95% CI, 1.12–2.95; P = 0.01) and cell cycle pathways (HR, 1.97; 95% CI, 1.15–3.37; P = 0.01), both of which stayed meaningful after multivariate adjustment.ConclusionsIn this study, we discovered shorter survival in midline glioma patients with PIK3CA and TERT mutations and with abnormal PI3K and cell cycle pathways. We also revealed a novel prognostic marker, MCL1 amplification that collectively provided new insights and opportunities in understanding and treating midline gliomas.

show abstract

“…Pediatric patients with diffuse brainstem pontine glioma (DIPG) were reported to have dismal prognosis and primarily treated with radiotherapy (RT), which was highly infiltrative and less amenable to surgery ( 3 , 4 ). Recent studies reported that pediatric DIPG was associated with H3K27M mutation, which was strongly suggested to be a developmental mutation confined to brainstem development ( 5 , 6 ). BSG without such typical appearances and mutations requires careful assessment as their age group and tumor grading may be highly informative about their amenability to surgical management and need for adjuvant therapy.…”

Section: Introductionmentioning

confidence: 99%

The Survival Benefits of Surgical Resection and Adjuvant Therapy for Patients With Brainstem Glioma

Liu

Feng

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

PurposeThe role of surgical resection in the treatment of brainstem glioma (BSG) is poorly understood. For pediatric low-grade (LGBSG) group, several monocentric small-scale retrospective studies reported contradictory conclusions. And there was no clinical study focused on surgical resection for adult or pediatric high-grade (HG) patient groups. This study aims to illustrate whether surgical resection and adjuvant therapy provide survival benefits for patients with histologically confirmed BSG.Patients and MethodsThis retrospective cohort study included 529 patients with histologically confirmed BSG in Surveillance Epidemiology and End Results (SEER) database from 2006-2015. Patients were divided into four groups by age and World Health Organization (WHO) grade. Kaplan-Meier curves of CSS were plotted by different treatment options to compare the survival probability. Univariate and multivariable analyses were then conducted to determine the prognosis effects of surgical resection and adjuvant therapy on cancer specific survival (CSS). All analyses were done in four different groups separately.ResultsThe final sample included 529 patients. The entire study population was divided into groups of pediatric LG (n=236, 44.6%), pediatric HG (n=37, 7.0%), adult LG (n=204, 38.6%) and adult HG (n=52, 9.8%). 52.7% (n=144) of pediatric patients had pilocytic astrocytoma and 45.3% (n=116) of adult patients had ependymoma. Pediatric LGBSG group had the highest gross total resection (GTR) rate (61.4%) and 5-year CSS rate (88.6%). Kaplan-Meier curves of pediatric LGBSG group revealed that patients treated with GTR had significantly better survival probability (P=0.033). Multivariable analysis identified GTR as independently significant predictor for prolonged CSS in pediatric LGBSG group (HR0.29, 95%CI 0.11-0.78, P=0.015); Surgical resection showed no relation to CSS in other patient groups. Kaplan-Meier curves of adult HGBSG group showed that patients treated with both RT and CT in adult HGBSG group had the best survival probability (P=0.02). However, multivariable analysis showed the combination of radiotherapy (RT) and chemotherapy (CT) was not significantly related to better CSS in adult HGBSG group (HR0.35, 95%CI 0.11-1.09, P=0.070). Adjuvant therapy didn’t associate with better CSS in other patient groups.ConclusionPediatric LGBSG group had the highest GTR rate and the most favorable clinical outcome. GTR can provide significant survival benefits for pediatric LGBSG group.

show abstract

The integrated genomic and epigenomic landscape of brainstem glioma

Cited by 58 publications

References 48 publications

Epidemiology and Survival of Patients With Brainstem Gliomas: A Population-Based Study Using the SEER Database

Epidemiology and Survival of Patients With Brainstem Gliomas: A Population-Based Study Using the SEER Database

Genomic Profiling Identified Novel Prognostic Biomarkers in Chinese Midline Glioma Patients

The Survival Benefits of Surgical Resection and Adjuvant Therapy for Patients With Brainstem Glioma

Contact Info

Product

Resources

About