Project description:Robust molecular subgrouping and copy-number profiling of medulloblastoma from small amounts of archival tumor material. Validation of patterns identified by whole-genome bisulphite sequencing in a larger cohort. DNA methylation profiles of 276 primary medulloblastoma and 8 normal cerebellum control samples were generated from fresh-frozen and formalin-fixed paraffin-embedded material using the Illumina 450k methylation array.
Project description:Smoothened (SMO)-inhibitors recently entered clinical trials for sonic-hedgehog driven medulloblastoma (SHH-MB). Clinical response appears highly variable. To understand the mechanism(s) of primary resistance and to identify pathways co-operating with aberrant SHH-signaling, we sequenced a large cohort of SHH-MBs across all age groups by sequencing, DNA methylation and expression profiling. Our data show that most adults but only half of the pediatric patients with SHH-MB will respond to SMO inhibition as predicted by molecular analysis of the primary tumor and tested in the SHH-xenografts, demonstrating that the next generation of SMO-inhibitor trials should be based on these predictive biomarkers. To further dissect the biological differences between the different age groups within SHH medulloblastomas, we looked at the DNA methylation profiles of SHH medulloblastoma samples.
Project description:Smoothened (SMO)-inhibitors recently entered clinical trials for sonic-hedgehog driven medulloblastoma (SHH-MB). Clinical response appears highly variable. To understand the mechanism(s) of primary resistance and to identify pathways co-operating with aberrant SHH-signaling, we sequenced a large cohort of SHH-MBs across all age groups by sequencing, DNA methylation and expression profiling. Our data show that most adults but only half of the pediatric patients with SHH-MB will respond to SMO inhibition as predicted by molecular analysis of the primary tumor and tested in the SHH-xenografts, demonstrating that the next generation of SMO-inhibitor trials should be based on these predictive biomarkers. To further dissect the biological differences between the different age groups within SHH medulloblastomas, we looked at the DNA methylation profiles of SHH medulloblastoma samples. We investigated the DNA methylation profiles of 46 SHH medulloblastomas across all age groups using the Illumina 450k methylation array.
Project description:Smoothened (SMO)-inhibitors recently entered clinical trials for sonic-hedgehog driven medulloblastoma (SHH-MB). Clinical response appears highly variable. To understand the mechanism(s) of primary resistance and to identify pathways co-operating with aberrant SHH-signaling, we sequenced a large cohort of SHH-MBs across all age groups by sequencing, DNA methylation and expression profiling. Our data show that most adults but only half of the pediatric patients with SHH-MB will respond to SMO inhibition as predicted by molecular analysis of the primary tumor and tested in the SHH-xenografts, demonstrating that the next generation of SMO-inhibitor trials should be based on these predictive biomarkers. To further dissect the biological differences between the different age groups within SHH medulloblastomas, we looked at the DNA methylation profiles of SHH medulloblastoma samples.
Project description:Smoothened (SMO)-inhibitors recently entered clinical trials for sonic-hedgehog driven medulloblastoma (SHH-MB). Clinical response appears highly variable. To understand the mechanism(s) of primary resistance and to identify pathways co-operating with aberrant SHH-signaling, we sequenced a large cohort of SHH-MBs across all age groups by sequencing, DNA methylation and expression profiling. Our data show that most adults but only half of the pediatric patients with SHH-MB will respond to SMO inhibition as predicted by molecular analysis of the primary tumor and tested in the SHH-xenografts, demonstrating that the next generation of SMO-inhibitor trials should be based on these predictive biomarkers. To further dissect the biological differences between the different age groups within SHH medulloblastomas, we looked at the DNA methylation profiles of SHH medulloblastoma samples. We investigated the DNA methylation profiles of 83 SHH medulloblastomas across all age groups using the Illumina 450k methylation array.
Project description:DNA methylation was generated from 11 pairs of matched primary-metastases medulloblastoma samples using the Illumina Infinium HumanMethylation450 BeadChip array
Project description:DNA methylation was generated from 11 pairs of matched primary-metastases medulloblastoma samples using the Illumina Infinium HumanMethylation450 BeadChip array Total DNA was extracted from primary and metastases medulloblastoma samples, bisulfite converted and hybridized to Illumina Infinium HumanMethylation450 BeadChip according to the manufacturer's instructions.