Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify. Herein leveraging a cohort of 2,336 patients spanning all disease stages, we characterize the genomic and clinical correlates of outcomes in PDAC. We show that a genomic subtype of KRAS wild-type tumors is associated with early disease onset, distinct somatic and germline features, and significantly better overall survival. Allelic imbalances at the KRAS locus are widespread. KRAS mutant allele dosage gains, observed in one in five…

• A
  Amgen
• EL
  Eli Lilly and Company
• A
  AstraZeneca
• F
  FibroGen
• RP
  Regeneron Pharmaceuticals
• TT
  TG Therapeutics
• PI
  Parker Institute for Cancer Immunotherapy
• AP
  Agios Pharmaceuticals
• BT
  Break Through Cancer
• TF
  Thompson Family Foundation
• B
  BeiGene
• I
  Incyte
• IB
  Innovent Biologics
• RM
  Revolution Medicines
• AF
  Applebaum Foundation
• E
  Eisai
• AP
  Astellas Pharma
• MO
  Ministry of Minority Affairs
• S
  Servier
• I
  Ipsen
• NI
  National Institutes of Health

  Award: P30CA008748
• G
  Genentech
• NC
  National Cancer Institute

  Awards: CA008748, CA257881-01A1, P30CA008748, P30 CA008748, P50 CA257881-01A1, R01 CA227534