MSK-IMPACT Clinical Sequencing Cohort (MSK, Nat Med 2017)

Overview

The foundational MSK-IMPACT clinical sequencing cohort (Zehir et al. 2017) comprising 10,000 tumor/normal pairs sequenced with the MSK-IMPACT targeted panel across tumor types. Within the cbio-kb corpus, this dataset is referenced as the institutional context for subsequent MSK rare-cancer profiling efforts PMID:36862133.

Composition

  • 10,000 prospective clinical cases across diverse tumor types profiled via MSK-IMPACT.

Assays / panels (linked)

Papers using this cohort

  • PMID:28481359 — Zehir et al., Nat Med 2017: Seminal MSK-IMPACT report; prospective CLIA-certified targeted sequencing of 10,945 tumors from 10,336 patients across 62 principal tumor types using IMPACT341/IMPACT410 panels; 36.7% of patients harbored an OncoKB-actionable alteration; 11% (527/5,009) matched to a genomically targeted clinical trial; full dataset deposited to cBioPortal as msk_impact_2017. PMID:28481359
  • PMID:36862133 — Doe-Tetteh et al. list msk_impact_2017 alongside [makeanimpact_ccr_2023](../datasets/makeanimpact_ccr_2023.md) as the cBioPortal dataset context for their rare-cancer Make-an-IMPACT outreach program, which itself used the MSK-IMPACT clinical platform to return results to patients and local physicians PMID:36862133.
  • PMID:39506116 — Kehl et al. MSK-CHORD: the 24,950-patient MSK-CHORD real-world dataset was built on top of MSK-IMPACT sequencing; msk_impact_2017 is cited as the foundational clinical sequencing backbone whose tumor genomics feed into MSK-CHORD PMID:39506116.
  • PMID:39746944 — Ziegler et al. MiMSI: the global comparison cohort (n=45,112 samples from 40,414 patients) drawn from prospective MSK-IMPACT clinical sequencing (January 2014–April 2020) is the same pipeline documented in msk_impact_2017; concordance between MSISensor and MiMSI was evaluated on this cohort PMID:39746944.

Notable findings derived from this cohort

  • TP53 was the most frequently altered gene (41% of 10,945 tumors, >10% in 43/62 principal tumor types); KRAS was 2nd (15%), with G12 codons comprising 80% of all KRAS mutations and 12% of all patients; 36.7% of patients harbored an OncoKB-actionable alteration. PMID:28481359
  • 81% of all mutations fell outside the combined target regions of commercially available amplicon hotspot panels; ≥9% of mutations would have been missed by WES to 150× mean depth, including targetable BRAF, EGFR, and MET alterations. PMID:28481359
  • Mutation-signature calling identified MMR deficiency (MSI) in 102 patients across 11 tumor types; 45% had not been previously tested, including a prostate cancer patient who responded to anti-PD-L1 therapy. PMID:28481359
  • 11% (527/5,009) of patients with ≥12-month follow-up were enrolled on a genomically matched targeted-therapy trial; 72% of matches occurred after MSK-IMPACT reporting itself. PMID:28481359
  • The original Make-an-IMPACT report demonstrates that the MSK-IMPACT clinical platform underpinning msk_impact_2017 can be extended via direct-to-patient outreach to enroll international rare-cancer cohorts with 86.8% sequencing success PMID:36862133.
  • Across 45,112 MSK-IMPACT samples from the same clinical sequencing pipeline, MiMSI reduced MSI-indeterminate calls from 3.8% (n=1,724 by MSISensor) to 0.47% (n=210), with 96% concordance for definitive MSS/MSI-H calls PMID:39746944.
  • The MSK-CHORD real-world dataset integrates MSK-IMPACT tumor genomics with NLP-derived EHR annotations for 24,950 patients; multimodal models combining genomic and NLP features outperformed stage-alone OS prediction in NSCLC, breast, colorectal, prostate, and pancreatic cancers PMID:39506116.
  • 706 advanced prostate cancers from MSK-IMPACT in this cohort were used as validation for 97 significantly mutated genes discovered in the prad_p1000 pan-1000 prostate meta-cohort, confirming novel drivers including CUL3 (9 cases), SPEN, SF3B1, and PIK3R2 PMID:29610475

Sources

  • cBioPortal study msk_impact_2017.

  • Zehir A, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017. PMID:28481359

  • PMID:29610475

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