Multiregion Whole Exome sequencing of paediatric High Grade Gliomas and DIPG

Paediatric High Grade Gliomas (pHGG) are defined by unique, specific and highly recurrent mutations in genes encoding histone H3 variants which mark robust subgroups with distinct age of onset, anatomical distribution, clinical outcome, histopathological and radiological features. We have used whole exome sequencing to identify the main recurrent somatic mutations occurring within pHGG including H3 histones and the coincident mutations and DNA copy number events in order to classify clinically relevant subgroups and the molecular events within them as new targets for therapy. Analysis of sequenced cases revealed multiple tumour subclones, spatially and temporally co-existing in a stable manner as observed by multiple sampling strategies.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 5 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001004114	The failure to develop effective therapies for paediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. Analysis of 142 sequenced cases revealed multiple tumour subclones, spatially and temporally co-existing in a stable manner as observed by multiple sampling strategies. This dataset provides multi region sequencing of high grade gliomas and diffuse intrinsic pontine gliomas from 15 patients. DNA was extracted from FFPE sections in 2-13 regions of each tumour and sequenced with Agilent SureSelect whole exome sequencing. Germline DNA was also sequenced in 14 cases. Data was aligned to hg19 with bwa and is provided as 79 separate BAM files.	Illumina HiSeq 2000	79

Publications	Citations
ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma. Koschmann C, Calinescu AA, Nunez FJ, Mackay A, Fazal-Salom J, Thomas D, Mendez F, Kamran N, Dzaman M, Mulpuri L, Krasinkiewicz J, Doherty R, Lemons R, Brosnan-Cashman JA, Li Y, Roh S, Zhao L, Appelman H, Ferguson D, Gorbunova V, Meeker A, Jones C, Lowenstein PR, Castro MG. Sci Transl Med 8: 2016 328ra28	165
ATRX mutations and glioblastoma: Impaired DNA damage repair, alternative lengthening of telomeres, and genetic instability. Koschmann C, Lowenstein PR, Castro MG. Mol Cell Oncol 3: 2016 e1167158	33
Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma. Koschmann C, Zamler D, MacKay A, Robinson D, Wu YM, Doherty R, Marini B, Tran D, Garton H, Muraszko K, Robertson P, Leonard M, Zhao L, Bixby D, Peterson L, Camelo-Piragua S, Jones C, Mody R, Lowenstein PR, Castro MG. Oncotarget 7: 2016 65696-65706	43
Multi-focal sequencing of a diffuse intrinsic pontine glioma establishes PTEN loss as an early event. Koschmann C, Farooqui Z, Kasaian K, Cao X, Zamler D, Stallard S, Venneti S, Hervey-Jumper S, Garton H, Muraszko K, Franchi L, Robertson PL, Leonard M, Opipari V, Castro MG, Lowenstein PR, Chinnaiyan A, Mody R. NPJ Precis Oncol 1: 2017 32	13
Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells. Vinci M, Burford A, Molinari V, Kessler K, Popov S, Clarke M, Taylor KR, Pemberton HN, Lord CJ, Gutteridge A, Forshew T, Carvalho D, Marshall LV, Qin EY, Ingram WJ, Moore AS, Ng HK, Trabelsi S, H'mida-Ben Brahim D, Entz-Werle N, Zacharoulis S, Vaidya S, Mandeville HC, Bridges LR, Martin AJ, Al-Sarraj S, Chandler C, Sunol M, Mora J, de Torres C, Cruz O, Carcaboso AM, Monje M, Mackay A, Jones C. Nat Med 24: 2018 1204-1215	100