Patients were enrolled on the PRecISion Medicine for Children with Cancer clinical trial (NCT03336931), as part of the Australian Zero Childhood Cancer (ZERO) Precision Medicine Program. ZERO is an Australian national paediatric precision medicine program currently focused on real time recruitment and analysis of patients with high-risk paediatric cancers (< 30% chance of survival). Informed consent was provided by the parents/legal guardian for participants under the age of 18 years and by participants over the age of 18 years15 (link). Eighty-nine patients diagnosed with brain tumours were enrolled on the ZERO clinical trial from September 2017 until May 2020. Amongst these patients, 28 were diagnosed with a H3K27M DMG and 39 with other high-grade glioma lacking the H3K27M mutation (HGG), including WHO grade III anaplastic astrocytoma and grade IV glioblastomas (GBM) irrespective of their anatomical location or their molecular profile besides the absence of H3K27M mutation15 (link). Out of the five cases presented in this study, two cases, zcc120 and zcc183 were previously reported in part15 (link).
The molecular profiling platform consisted of germline and tumour whole genome sequencing (WGS) associated with matched germline DNA WGS, tumour only RNA-sequencing and tumour DNA Infinium MethylationEPIC array (Illumina). DNA and RNA were extracted from fresh, fresh frozen or cryopreserved tumour tissue and matched germline samples (from either fresh, cryopreserved or fresh frozen peripheral blood or skin) at the Children’s Cancer Institute (Australia), as described previously15 (link). WGS was conducted at the Kinghorn Centre for Clinical Genomics at the Garvan Institute of Medical Research (Australia), DNA methylation array performed by the Australian Genome Research Facility and transcriptome sequencing performed at Murdoch Children’s Research Institute (Australia).
Additional cohorts were used in this study from Mondal et al.7 (link) GSE140124 (N = 9 H3-WT cases) and Castel et al.6 (link) E-MTAB-8888 (N = 14 H3-WT and N = 25 H3.3-K27M and H3.1-K27M mutant cases).
The molecular profiling platform consisted of germline and tumour whole genome sequencing (WGS) associated with matched germline DNA WGS, tumour only RNA-sequencing and tumour DNA Infinium MethylationEPIC array (Illumina). DNA and RNA were extracted from fresh, fresh frozen or cryopreserved tumour tissue and matched germline samples (from either fresh, cryopreserved or fresh frozen peripheral blood or skin) at the Children’s Cancer Institute (Australia), as described previously15 (link). WGS was conducted at the Kinghorn Centre for Clinical Genomics at the Garvan Institute of Medical Research (Australia), DNA methylation array performed by the Australian Genome Research Facility and transcriptome sequencing performed at Murdoch Children’s Research Institute (Australia).
Additional cohorts were used in this study from Mondal et al.7 (link) GSE140124 (N = 9 H3-WT cases) and Castel et al.6 (link) E-MTAB-8888 (N = 14 H3-WT and N = 25 H3.3-K27M and H3.1-K27M mutant cases).
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