Colorectal Adenocarcinoma (TCGA, Nature 2012)

Overview

The TCGA colorectal cancer dataset comprises 276 colorectal carcinoma tumor/normal pairs collected as part of The Cancer Genome Atlas project. It is the landmark comprehensive molecular characterization of colorectal adenocarcinoma, covering COADREAD (colon and rectal cancers together). Samples were collected from multiple institutions and subjected to multi-platform molecular profiling including exome sequencing, low-pass WGS, copy-number arrays, methylation profiling, and gene expression.

Composition

  • 276 colorectal carcinoma tumor/normal pairs
  • Cancer type: COADREAD (colorectal adenocarcinoma)
  • 224 pairs analyzed by whole-exome sequencing; 97 by low-pass whole-genome sequencing (~3-4X)
  • 257 tumors profiled for somatic copy-number alterations with Affymetrix SNP 6.0 arrays
  • 236 tumors profiled for promoter DNA methylation (Illumina HumanMethylation27)
  • mRNA expression (Agilent microarrays + RNA-Seq), miRNA expression
  • 16% of tumors classified as hypermutated; 84% non-hypermutated

Assays / panels (linked)

Papers using this cohort

Notable findings derived from this cohort

  • 24 significantly mutated genes identified including APC (81%), TP53 (60%), KRAS (43%), PIK3CA (18%), and novel candidates ARID1A, SOX9, AMER1 PMID:22810696
  • 16% of CRCs are hypermutated; of these 75% are MSI-H with MLH1 methylation/CIMP, 25% have somatic mismatch-repair or POLE mutations PMID:22810696
  • Non-hypermutated colon and rectal cancers are genomically indistinguishable by copy number, methylation, mRNA, and miRNA patterns PMID:22810696
  • WNT signaling pathway altered in 93% of all tumors; ERBB2 amplification (4%) identified as potentially targetable with trastuzumab PMID:22810696

Sources

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