Medulloblastoma — PCGP WGS (mbl_pcgp)

Overview

A cohort of 93 medulloblastoma tumors assembled by the Pediatric Cancer Genome Project (PCGP), a collaboration between St. Jude Children’s Research Hospital and Washington University. The discovery cohort comprised 37 medulloblastomas with matched normal blood subjected to whole-genome sequencing. A validation cohort of 56 additional medulloblastomas underwent targeted sequencing of 136 candidate genes. Tumors span all four molecular subgroups: WNT, SHH, subgroup-3, and subgroup-4. Data deposited in dbGaP (phs000409) and SRA (SRP008292).

Composition

  • Discovery cohort: 37 tumors — WNT (n=5), SHH (n=5), subgroup-3 (n=6), subgroup-4 (n=19), unclassified (n=2).
  • Validation cohort: 56 tumors — WNT (n=6), SHH (n=8), subgroup-3 (n=11), subgroup-4 (n=19), unclassified (n=12).
  • Cancer type: MBL (medulloblastoma, pediatric).
  • Key clinical fields: molecular subgroup, sex (relevant for KDM6A/UTY on chrY).

Assays / panels (linked)

  • whole-genome-seq — discovery cohort, 37 tumors; detected 22,887 validated somatic mutations, 536 SVs, and 5,802 CNVs.
  • affymetrix-snp6 — copy-number analysis.
  • sanger-sequencing — validation of candidate mutations.
  • Affymetrix U133v2 — mRNA expression profiling.
  • Custom capture arrays — targeted validation cohort.

Papers using this cohort

  • PMID:22722829 — Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations (Robinson et al., 2012).

Notable findings derived from this cohort

  • 49 genes recurrently mutated across all 93 tumors; 41 (84%) were novel for medulloblastoma PMID:22722829.
  • KDM6A inactivating mutations in 8/93 tumors (predominantly subgroup-4 males); co-deletion of UTY on chrY in 57% of KDM6A-mutant males PMID:22722829.
  • DDX3X DEAD-box domain mutations enriched in WNT subgroup (p<0.0001); alters RNA binding and expands LRLP lineage PMID:22722829.
  • SMARCA4 helicase-domain missense mutations in 4 WNT tumors (p<0.002) PMID:22722829.
  • CTNNB1 stabilizing mutations in 8/11 WNT tumors (p<0.0001) PMID:22722829.
  • PIK3CA activating mutations in 3 tumors; accelerates but does not initiate WNT-medulloblastoma in mouse models PMID:22722829.

Sources

This page was processed by entity-page-writer on 2026-05-06.