MSK PDAC Prospective Sequencing Cohort (2024)

Overview

Prospective institutional cohort of 2,336 patients with pancreatic ductal adenocarcinoma (PDAC) sequenced with MSK-IMPACT at Memorial Sloan Kettering between January 2014 and September 2021. Deep clinical curation was performed for 1,480 patients (63%). Released as cBioPortal study pdac_msk_2024 by Varghese, Perry et al. 2025 PMID:39753968.

Composition

  • 2,336 patients with PAAD; stage distribution: 731 resectable (31%), 581 borderline-resectable/locally advanced (25%), 1,024 metastatic (44%); median OS 31/19/11 months respectively PMID:39753968.
  • Sample type: 1,424 (61%) primary tumor, 912 (39%) metastasis; median age 67 years (range 24–93) PMID:39753968.
  • 1,480 patients (63%) with manually curated treatment history, time on treatment, and best-response data from medical records PMID:39753968.
  • Allele-specific copy number inferred with FACETS v0.5.14 in 1,555/2,322 tumors passing QC PMID:39753968.

Assays / panels (linked)

Papers using this cohort

  • PMID:39753968 — Varghese, Perry et al. 2025: Defines three genomic subtypes of PDAC (KRAS-mutant 95%, other-MAPK-mutant 3%, MAPK-WT 2%); characterizes KRAS mutant-allele dosage gains as a prognostic biomarker independent of stage; shows G12R confers better OS than G12D (HR_adj=0.78, P=0.003).

Notable findings derived from this cohort

  • Three genomic subtypes: KRAS-mutant (n=2,209, 95%), other-MAPK-mutant (n=76, 3%), and MAPK-WT (n=51, 2%); other-MAPK-mutant and MAPK-WT subtypes had longer OS than KRAS-mutant (HR_adj=0.69, P=0.014 and P=0.041 respectively) PMID:39753968.
  • KRAS allele distribution: G12D 41%, G12V 32%, G12R 16%, G12C 1%, Q61H 1%; G12R associated with better OS than G12D (HR_adj=0.78, 95% CI 0.67–0.92, P=0.003) PMID:39753968.
  • Allelic imbalance at KRAS in 42% of KRAS-mutant tumors with quality copy-number data; 93% of imbalance events preferentially gained/retained the mutant allele PMID:39753968.
  • KRAS mutant-allele dosage gains (non-WGD subset, n=934) independently predicted shorter OS (HR_adj=1.7, 95% CI 1.4–2.0, P=3.5×10⁻⁷) across all clinical stages PMID:39753968.
  • 10% of patients carried pathogenic germline variants: BRCA2 3.7%, BRCA1 1.8%, ATM 1.8%, PALB2 0.5%; Lynch syndrome in 0.7% (17 patients), 6/17 MSI-H PMID:39753968.
  • ~10% of patients harbored OncoKB level 1 or 2 biomarkers; additional 78% met level 3A based on KRAS G12D/V/R/A/S PMID:39753968.
  • RNF43 alterations independently associated with shorter first-line OS (HR_adj=2.79, P_adj=0.047); AKT2 amplifications associated with shorter OS in metastatic, chemotherapy-treated patients (HR_adj=2.03, P_adj=0.048) PMID:39753968.

Sources

  • cBioPortal study pdac_msk_2024. Varghese AM, Perry MA, et al. Genomic subtypes and allelic imbalance of KRAS in pancreatic ductal adenocarcinoma. 2025. PMID:39753968.

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