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. 2025 Nov 17:17:17588359251339939.
doi: 10.1177/17588359251339939. eCollection 2025.

Characteristics of KRAS WT pancreatic adenocarcinomas: results of a large French multicentric cohort

Noémie Trystram  1 , Jérome Cros  2 , Hélène Blons  1   3 , Simon Garinet  3 , Rémy Nicolle  4 , Delphine Le Corre  1 , Shu Lin Zhao  5 , Jim Biagi  6 , Alexandre Harlé  7 , Thierry Conroy  8 , Vinciane Rebours  9 , Julien Taïeb  1   10 , Laetitia Dahan  11 , Pierre Laurent-Puig  1   12 , Jean-Baptiste Bachet  13   1
Affiliations

Characteristics of KRAS WT pancreatic adenocarcinomas: results of a large French multicentric cohort

Noémie Trystram et al. Ther Adv Med Oncol. .

Abstract

Background: Genome and transcriptome analysis has enhanced the characterisation of pancreatic ductal adenocarcinoma (PDAC), paving the way for targeted therapies. Tumours KRAS wild type (WT) represent a unique subgroup.

Objectives: Characterise the population and molecular abnormalities present in KRAS WT PDAC.

Design: Clinical and molecular data from a large retrospective cohort of KRAS WT PDAC were analysed.

Methods: Next-generation sequencing (NGS) was used to analyse DNAs and RNAs, allowing molecular and transcriptomic characterisation.

Results: We identified 93/1059 (9%) KRAS WT PDAC, among which eight had druggable fusions (n = 8/30 contributive samples), six had BRAF mutations and 19 (n = 19/47) had mutations in homologous recombination (HR) pathway genes. Potential molecular targets in this series may be underestimated due to many non-contributive results. Clinical characteristics and survival did not differ between patients with KRAS WT and KRAS-mutated tumours. Transcriptomic data were available for 350 samples. Their analysis shows a difference in phenotype between mutated and WT tumours, with a molecular profile that appears to be better prognostic for KRAS WT tumours.

Conclusion: KRAS WT tumours are enriched with molecular abnormalities of therapeutic interest. These include oncogene driver alterations (gene fusions and mutations) and mutations in genes of the HR pathway. Targeted therapy strategies for PDAC rely on molecular testing beyond RAS, but further research is needed to identify new therapeutic approaches that improve outcomes in PDAC.

Keywords: KRAS mutation; genomics; molecular profiling; next-generation sequencing; pancreatic cancer.

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Conflict of interest statement

P.L.-P. received honorarium from Biocartis, Amgen, Pierre Fabre Servier for consulting. J.-B.B. received personal fees from Abbvie, Amgen, Bayer, Bristol Myers Squibb, GSK, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Sanofi, Servier, Takeda and non-financial support from Amgen, Merck Serono and Roche, outside the submitted work.

Figures

Figure 1.
Figure 1.
Flow chart. (a) Cohort and molecular analyses. (b) Methods for determining KRAS mutations, fusion genes and other mutations.
Figure 2.
Figure 2.
Survival curves. (a) Recurrence-free survival according to KRAS status in patients with resected tumours. (b) OS according to KRAS status in patients with resected tumours. (c) OS according to KRAS status in patients with metastatic tumours. OS, overall survival.
Figure 3.
Figure 3.
Transcriptomic analysis. (a) KRAS pathways. (b) Volcano plot representing differential gene analysis.
See this image and copyright information in PMC

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