Medulloblastoma (Broad, Nature 2012)
Overview
The Broad medulloblastoma dataset comprises 92 primary medulloblastoma tumor/normal pairs from pediatric patients, profiled by whole-exome sequencing (Pugh et al., Nature 2012). Samples were collected from Children’s Hospital Boston, Hospital for Sick Children Toronto, and Children’s Oncology Group/CHTN. The cohort spans all four molecular subgroups of medulloblastoma (WNT, SHH, Group 3, Group 4) and is characterized by one of the lowest somatic mutation rates across cancer types (median 0.35/Mb), consistent with other pediatric tumors.
Composition
- 92 primary medulloblastoma tumor/normal pairs
- Cancer type: MBL (medulloblastoma)
- Molecular subgroups: 6 WNT, 23 SHH, 33 Group 3, 30 Group 4
- Median age and institutional breakdown not specified but samples from three major pediatric oncology centers
- Median somatic mutation rate: 0.35 non-silent mutations per megabase (median 12 non-silent mutations per tumor)
Assays / panels (linked)
- whole-exome-seq — hybrid capture of 193,094 exons from 18,863 genes; median 106X coverage
- mutsig — significance testing for somatic mutations (q < 0.1 threshold)
- Validation: microfluidic PCR (Fluidigm) + single-molecule real-time sequencing (Pacific Biosciences); 19/20 mutations confirmed
Papers using this cohort
- PMID:22820256 — Pugh et al. Nature 2012 primary analysis
Notable findings derived from this cohort
- 12 genes significantly mutated (q<0.1): CTNNB1, PTCH1, KMT2D (MLL2), DDX3X, GPS2, TP53, KDM6A, BCOR, SMARCA4, LDB1, CTDNEP1, CSNK2B PMID:22820256
- DDX3X mutated in 7 tumors (half of WNT subgroup, p=0.005); potentiates mutant beta-catenin transcriptional activity PMID:22820256
- N-CoR complex genes (GPS2, BCOR, LDB1) identified as recurrently mutated — novel finding in medulloblastoma PMID:22820256
- Histone methyltransferase gene set enriched for somatic mutations across 21 tumors (q=5.8e-9) PMID:22820256
- Older patients (16-31 years) had significantly higher mutation frequency (p=7.7e-5, Wilcoxon rank-sum test) PMID:22820256
Sources
- PMID:22820256 — Pugh et al. Nature 2012
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