MSK Resected PDAC KRAS-Allele Cohort (2024)

Overview

Single-institution retrospective cohort of 1,360 consecutive patients with pancreatic ductal adenocarcinoma who underwent surgical resection at Memorial Sloan Kettering between April 2004 and April 2019, assembled to interrogate KRAS allele–specific clinical outcomes and biology in PAAD PMID:39214094.

Composition

  • 1,360 resected PDAC patients; 397 (29%) stage I, 963 (71%) stage II–III; OS of the full cohort 30.7 months (95% CI 28.0–32.8) PMID:39214094.
  • Tumor targeted sequencing on MSK-IMPACT in 397 patients (103 stage I, 294 stage II–III) with no sequencing selection criteria PMID:39214094.
  • Bulk RNA-seq on 100 resected tumors and high-plex spatial profiling on 20 patients (14 tumors, 6 normal) using NanoString CosMx SMI tissue microarrays PMID:39214094.
  • 22% of the sequenced subset received neoadjuvant therapy (most commonly 5-FU–based regimens, frequently FOLFIRINOX); 82% received adjuvant therapy PMID:39214094.

Assays / panels (linked)

  • MSK-IMPACT — targeted tumor sequencing, used for driver-gene and KRAS-allele calls across the 397-patient sequenced subset PMID:39214094.
  • CosMx SMI — NanoString high-plex spatial molecular imaging on TMAs for the 20-patient spatial subcohort PMID:39214094.

Papers using this cohort

  • PMID:39214094 — McIntyre et al., Cancer Cell 2024. KRASG12R enrichment in early-stage PDAC with distinct clinical outcomes and NF-κB-biased transcriptional program.

Notable findings derived from this cohort

  • KRAS altered in 90%, TP53 71%, CDKN2A 24%, SMAD4 17%; KRAS allele distribution G12D 36.5% / G12V 32.5% / G12R 13.9% / other 8.1% / WT 9.1% PMID:39214094.
  • KRASG12R enriched in stage I disease (23% vs 11%), more often node-negative (47% vs 26% for G12D), and associated with improved OS and reduced distant recurrence PMID:39214094.
  • KRASG12R tumors carry a higher frequency of CDKN2A mutations than KRASG12D (40% vs 22.1%) PMID:39214094.

Sources

  • cBioPortal study: https://www.cbioportal.org/study/summary?id=pancreas_msk_2024

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