Dataset Information

The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma.

ABSTRACT: Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem.

SUBMITTER: Wu G

PROVIDER: S-EPMC4056452 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma.

Wu Gang G Diaz Alexander K AK Paugh Barbara S BS Rankin Sherri L SL Ju Bensheng B Li Yongjin Y Zhu Xiaoyan X Qu Chunxu C Chen Xiang X Zhang Junyuan J Easton John J Edmonson Michael M Ma Xiaotu X Lu Charles C Nagahawatte Panduka P Hedlund Erin E Rusch Michael M Pounds Stanley S Lin Tong T Onar-Thomas Arzu A Huether Robert R Kriwacki Richard R Parker Matthew M Gupta Pankaj P Becksfort Jared J Wei Lei L Mulder Heather L HL Boggs Kristy K Vadodaria Bhavin B Yergeau Donald D Russell Jake C JC Ochoa Kerri K Fulton Robert S RS Fulton Lucinda L LL Jones Chris C Boop Frederick A FA Broniscer Alberto A Wetmore Cynthia C Gajjar Amar A Ding Li L Mardis Elaine R ER Wilson Richard K RK Taylor Michael R MR Downing James R JR Ellison David W DW Zhang Jinghui J Baker Suzanne J SJ

Nature genetics 20140406 5

Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-H ...[more]

PMID: 24705251

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Project description:Background and purposeThe conventional MR imaging appearance of diffuse intrinsic pontine glioma suggests intralesional histopathologic heterogeneity, and various distinct lesion components, including T2-hypointense foci, have been described. Here we report the prevalence, conventional MR imaging semiology, and advanced MR imaging features of non-necrotic T2-hyperintense foci in diffuse intrinsic pontine glioma.Materials and methodsTwenty-five patients with diffuse intrinsic pontine gliomas were included in this study. MR imaging was performed at 3T by using conventional and advanced MR imaging sequences. Perfusion (CBV), vascular permeability (ve, Ktrans), and diffusion (ADC) metrics were calculated and used to characterize non-necrotic T2-hyperintense foci in comparison with other lesion components, namely necrotic T2-hyperintense foci, T2-hypointense foci, peritumoral edema, and normal brain stem. Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon rank sum tests.ResultsSixteen non-necrotic T2-hyperintense foci were found in 12 tumors. In these foci, ADC values were significantly higher than those in either T2-hypointense foci (P = .002) or normal parenchyma (P = .0002), and relative CBV values were significantly lower than those in either T2-hypointense (P = .0002) or necrotic T2-hyperintense (P = .006) foci. Volume transfer coefficient values in T2-hyperintense foci were lower than those in T2-hypointense (P = .0005) or necrotic T2-hyperintense (P = .0348) foci.ConclusionsNon-necrotic T2-hyperintense foci are common, distinct lesion components within diffuse intrinsic pontine gliomas. Advanced MR imaging data suggest low cellularity and an early stage of angioneogenesis with leaky vessels resulting in expansion of the extracellular space. Because of the lack of biopsy validation, the underlying histoarchitectural and pathophysiologic changes remain unclear; therefore, these foci may correspond to a poorly understood biologic event in tumor evolution.

Dataset Information

The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma.

Publications

The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma.

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