Merged Cohort of LGG and GBM (TCGA, Cell 2016)

Overview

The TCGA pan-glioma merged dataset (lgggbm_tcga_pub) integrates the lgg_tcga (516 lower-grade glioma samples, WHO grades II–III) and gbm_tcga (606 GBM samples, WHO grade IV) cohorts into a single 1,122-patient resource. The primary publication by Ceccarelli et al. 2016 uses this merged resource for integrated analysis of exome sequencing, RNA-seq, DNA copy number, DNA methylation (27K+450K), and RPPA data to define a molecular taxonomy of adult diffuse glioma that supersedes WHO histological classification. PMID:26824661

Composition

  • 1,122 newly diagnosed adult diffuse glioma patients: 516 LGG (grades II–III) + 606 GBM (grade IV).
  • Histology: 590 GBM (56%), 174 oligodendroglioma (17%), 169 astrocytoma (16%), 114 oligoastrocytoma (11%).
  • Clinical data available for 1,046/1,122 (93%) cases.
  • Cancer types: DIFG (umbrella), GBM, ASTR, ODG. PMID:26824661

Assays / panels (linked)

  • Gene expression: n=1,045.
  • DNA copy number: n=1,084.
  • DNA methylation: n=932 (HM27 for 287 GBM; HM450 for 516 LGG + 129 GBM).
  • Exome sequencing: n=820 (513 LGG + 307 GBM); mutation calling by MuTect, Indelocator, VarScan, RADIA (≥2-caller consensus); SMGs by MutSig (MutSigCV).
  • RPPA: n=473.
  • WGS available for telomere-length and TERT-promoter analyses.
  • Copy number by GISTIC (GISTIC2); fusions by PRADA and deFuse. PMID:26824661

Papers using this cohort

  • PMID:26824661 — Ceccarelli et al. 2016, Cell: Primary integrative pan-glioma study defining 75 significantly mutated genes, six DNA-methylation subtypes (LGm1–6), PA-like IDH-wildtype glioma, and G-CIMP-low as a high-risk IDH-mutant subgroup.

Notable findings derived from this cohort

  • 75 significantly mutated genes (SMGs) identified across 1,122 gliomas, of which 45 had not been previously associated with glioma; mutation frequencies for novel SMGs ranged from 0.5% to 2.6%. PMID:26824661
  • Pan-glioma DNA methylation clustering of 932 samples yields six clusters (LGm1–6): LGm1/2/3 are IDH-mutant (99%) and LGm4/5/6 are IDH-wildtype (99%), with RNA-seq yielding four expression clusters (LGr1–4). PMID:26824661
  • G-CIMP-low: a newly defined IDH-mutant non-codel subgroup with reduced genome-wide methylation and poor survival (comparable to IDH-wildtype); 15/18 G-CIMP-low cases carry cell-cycle pathway abnormalities (CDK4, CDKN2A). PMID:26824661
  • PA-like IDH-wildtype LGG: a favorable-prognosis IDH-wildtype subtype with MAPK-pathway alterations (BRAF, NF1, NTRK1/NTRK2, FGFR1/FGFR2) in 52% of cases and low TERT expression (8%); younger patients (mean 37.6 vs 50.8 yr). PMID:26824661
  • ATRX, not TERT promoter, drives telomere lengthening: ATRX-mutant gliomas have significantly longer telomeres (t-test p<0.0001) consistent with ALT mechanism. PMID:26824661
  • Cohesin pathway (NIPBL, STAG2) disrupted in 16% of LGG/GBM — nominated as a therapeutic vulnerability for PARP inhibitors. PMID:26824661
  • Methylation subtype is independently prognostic (C-index 0.836 with age + grade + epigenetic subtype; LRT p<0.0001); outperforms histology-based and TERT-based classifiers. PMID:26824661

Sources

  • cBioPortal study: lgggbm_tcga_pub — https://www.cbioportal.org/study/summary?id=lgggbm_tcga_pub
  • Component cohorts: lgg_tcga (516 LGG), gbm_tcga (606 GBM).
  • PMID:26824661 — Ceccarelli et al. 2016, Cell, DOI 10.1016/j.cell.2015.12.028.

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