Colon Adenocarcinoma (COAD)

Overview

Colon Adenocarcinoma is a Colorectal Cancer (parent COADREAD).

Cohorts in the corpus

  • coad_silu_2022: 348 treatment-naive primary colon cancer patients (AC-ICAM) with matched tumor and healthy colon tissue, profiled by RNA-seq, WES, deep TCRβ-seq, 16S rRNA-seq, and tumor WGS; median follow-up 4.6 years PMID:37202560.
  • coadread_tcga used as a comparator PMID:37202560.
  • HCT-116 (HER2−, COAD cell line): negative-control model in ADC radiosensitization study — T-DM1 IC50 >100 nM and no tumor-growth benefit from adding T-DM1 to IR in HCT-116 xenografts, demonstrating receptor-selectivity of the approach. PMID:27698471

Recurrent alterations

  • No single driver gene is proposed as a biomarker; the paper’s gene-level claims focus on the 20-gene Immunologic Constant of Rejection (ICR) module PMID:37202560.
  • ERBB2 (HER2): HCT-116 is HER2− (T-DM1 IC50 >100 nM), serving as the definitive HER2-negative colon cancer negative control demonstrating receptor-selectivity of ADC radiosensitization. PMID:27698471
  • The ICR signature includes IFNG, TBX21, CD8A, CD8B, IL12B, STAT1, IRF1, CCL5, CXCL9, CXCL10, GNLY, PRF1, GZMA, GZMB, GZMH, CD274, CTLA4, FOXP3, IDO1, PDCD1 PMID:37202560.
  • NCI-60 CellMiner pharmacogenomics analysis identified ABCB1 expression and EGFR pathway activity as determinants of drug sensitivity in colon cancer cell lines PMID:22802077
  • 74-tumor WES cohort of colorectal adenocarcinoma (Genentech) identified RSPO2/RSPO3 fusions mutually exclusive with APC mutations, implicating Wnt pathway activation as a universal driver PMID:22895193
  • In 69 matched MSS colorectal cancer primary/metastasis trios (40% right colon, 44% left colon), KRAS/NRAS/BRAF status was 100% concordant, supporting use of either primary or metastatic biopsy for clinical RAS/RAF testing. PMID:25164765
  • Whole-exome and targeted resequencing of 103 MSS COAD from African Americans identified 20 new significantly mutated genes, including EPHA6 and FLCN as AA-specific driver candidates, with a ~twofold higher mutation rate per tumor versus 129 Caucasian CRCs (P<0.001). PMID:25583493
  • In the MSK-IMPACT pan-cancer cohort, KRAS was mutated in 44% of COAD (90% in PAAD); POLE and MMR mutation signatures predominated in colorectal cancer alongside elevated MSI rates; MSI COAD patients showed responses to immune checkpoint blockade. PMID:28481359
  • In MSK-IMPACT sequencing of 1,134 CRCs, colon cancer showed enrichment for KRAS, BRAF, PIK3CA, RNF43, and SMAD4 alterations in right-sided versus left-sided tumors; 37% of left-sided MSS mCRC lacked detectable mitogenic-pathway mutations, suggesting ligand-driven RTK activation PMID:29316426
  • In the SUMMIT basket trial (n=12 colorectal), HER2-mutant colon cancer showed no RECIST responses to neratinib, consistent with lineage-based resistance; the study speculates combination HER-targeted therapy may be needed to overcome this resistance PMID:29420467
  • MC3 pan-cancer mutation-calling project (10,510 TCGA pairs) included COAD; concordance with PanCan12 MAF exceeded 90%; MSI-high colorectal tumors are prominent hypermutators in the MC3 dataset PMID:29596782
  • Pan-cancer fusion study (9,624 TCGA samples) included COAD as one of 33 cancer types in the pan-cancer cohort PMID:29617662
  • Pan-cancer aneuploidy study placed COAD in the gastrointestinal arm-level cluster (co-gaining 8q, 13q, chromosome 20 alongside READ, STAD, PAAD); COAD and READ are exceptions to the positive aneuploidy–mutation-rate correlation due to MSI-high and POLE-mutant cases PMID:29622463

Subtypes

  • ICR consensus clustering segregates tumors into ICR-high (hot), ICR-medium, and ICR-low (cold) PMID:37202560.
  • ICR outperforms consensus molecular subtype (CMS) and MSI classifications for prognosis and retains prognostic value within the CMS4/mesenchymal subtype PMID:37202560.
  • ICR prognostic effect: ICR-high vs ICR-low HR=0.54 (95% CI 0.34–0.86, P=0.0095); ICR-medium vs ICR-low HR=0.63 (0.43–0.91, P=0.014) PMID:37202560.
  • Quantifying genetic immunoediting further refines ICR’s prognostic value PMID:37202560.
  • A Ruminococcus bromii-driven microbiome signature combined with ICR (mICRoScore) identifies patients with excellent survival probability PMID:37202560.

Therapeutic landscape

  • Paper does not directly test predictive utility for immunotherapy in colon cancer PMID:37202560.
  • HCT-116 (HER2−) colon xenografts showed no benefit from T-DM1 + IR vs. IR alone, confirming that receptor expression is required for ADC-mediated radiosensitization. PMID:27698471
  • TRIM24-BRAF fusions identified in 43% of BRAF-fusion-positive colorectal cases; frequent co-mutations include RNF43 (64%), TP53 (57%), KMT2D (43%), MSH3 (42%), and ARID1A (36%) PMID:38922339.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22802077

This page was processed by crosslinker on 2026-05-14. - PMID:22895193

This page was processed by crosslinker on 2026-05-14. - PMID:25164765

This page was processed by crosslinker on 2026-05-14. - PMID:25583493

This page was processed by entity-page-writer on 2026-05-15. - PMID:29316426 - PMID:29420467

This page was processed by entity-page-writer on 2026-05-15. - PMID:29596782

This page was processed by wiki-cli on 2026-05-15. - PMID:29617662

This page was processed by wiki-cli on 2026-05-15. - PMID:29622463

This page was processed by wiki-cli on 2026-05-15.