OncoKB Annotation

Overview

A bioinformatics annotation step in which somatic variants identified by tumor sequencing are classified against the Memorial Sloan Kettering OncoKB precision oncology knowledge base (oncokb.org). OncoKB assigns evidence-based actionability levels (Level 1–4) to alterations based on FDA approvals, clinical trial data, and biological evidence. The annotation provides structured therapeutic implication tiers enabling prioritization of variants for clinical management or trial enrollment.

Used by

  • OncoKB database (accessed 6 January 2017) used to classify potentially oncogenic and actionable mutations in 19 anaplastic oligodendroglioma tumors from the odg_msk_2017 cohort (MSK-IMPACT 410-gene panel); identified Level 2B alterations (CDK4 amplification, TSC1) and Level 3B alterations (IDH1 R132H, IDH2 R172K, KRAS Q61H, PIK3CA) PMID:28472509.
  • Applied to MSK-IMPACT-profiled prostate cancer alterations (504 tumors from 451 patients) to identify actionable alterations; 36% of patients carried at least one potentially actionable alteration per OncoKB PMID:28825054
  • OncoKB used to annotate oncogenic effect of alterations in 295 metastatic EGC patients; 53% had at least one OncoKB-defined potentially actionable alteration PMID:29122777
  • OncoKB actionability rates: 86% of MSI-H/hypermutated vs 37% of MSS metastatic COADREAD carried potentially actionable alterations (p<0.001) in the 1,134-tumor MSK-IMPACT cohort PMID:29316426
  • OncoKB (Sept 2017) used for pathway-level oncogenicity calls in SUMMIT basket-trial patients with ERBB2/ERBB3-mutant tumors; contributed to co-mutation pathway analysis PMID:29420467
  • OncoKB used to rescue genes with ≥5 oncogenic variants from MutSig2CV in the prostate prad_p1000 analysis; supplemented statistical significance filtering PMID:29610475

Notes

  • OncoKB actionability tiers: Level 1 (FDA-recognized biomarker with approved therapy in this tumor type), Level 2 (standard care or FDA-recognized in another tumor type), Level 3 (clinical evidence), Level 4 (compelling biological evidence).
  • Annotation is database-version-dependent; therapeutic implications evolve as new trial data accrue (e.g., KRAS G12C was unactionable at time of early MSK-IMPACT publications but gained Level 1 evidence post-approval of sotorasib).
  • Distinct from the OncoKB programmatic annotation tool (see oncokb) used in MSK-IMPACT routine pipeline; this page captures the variant-classification annotation step as applied in specific papers.

Sources

  • PMID:28472509 — Thomas et al., MSK HDC-ASCT phase II trial in anaplastic oligodendroglioma; OncoKB-classified actionable variants in 19 tumor exomes.

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