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Results of a multigene panel testing approach targeting patients with suspected genetic predisposition to pancreatic ductal adenocarcinoma

European Journal of Human Genetics (2026)Cite this article

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Abstract

Pancreatic ductal adenocarcinoma occur in the context of a suspected or proven genetic predisposition in 5–10% of cases. While universal germline multigene panel testing is currently recommended by NCCN and ASCO, this approach was previously limited to patients with personal and/or family criteria suggestive of hereditary predisposition. We report the results of this « selective » approach applied in our institution from January 2018 to June 2023. Germline testing of a panel of 13 « clinically actionable » genes (APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51C, RAD51D, STK11) was performed in 496 patients with pancreatic ductal adenocarcinoma and suspected genetic predisposition based on the validation of prespecified clinical criteria. A germline pathogenic/likely pathogenic variant of one of these genes was identified in 49 patients corresponding to 9.9% of the study population. ATM and BRCA2 were the two most frequently implicated genes (18 and 16 cases, respectively) and the prevalence of pathogenic/likely pathogenic variants of these genes was significantly higher than in gnomAD controls. The overall contribution of core and non-core genes of the Homologous Recombination DNA repair system was 83.7% while the contribution of the Mismatch Repair system was 10.2%. An exploratory approach consisting of unmasking the results of the NGS analysis of 123 « research » genes involved in the carcinogenesis was applied to the 447 patients tested negative for the different genes of our diagnostic panel. This approach failed to identify other susceptibility genes to pancreatic adenocarcinoma.

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The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This study did not benefit from financial support.

Author information

Authors and Affiliations

  1. Department of Genetics, PSL Research University, Paris, France

    Bruno Buecher, Mathilde Warcoin, Emilie Rolland, Rukhshona Abdullazoda, Aurélia Le Guillevic, Chrystelle Colas & Lisa Golmard

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  1. Bruno Buecher
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All authors were involved in drafting the manuscript, have read and approved the final paper and agree to be accountable to all aspects of this work

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Correspondence to Bruno Buecher.

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All patients included in this study provided written informed consent for MGPT as well as for additional exploratory research analyses. In this context, approval by an ethics committee was not required.

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Buecher, B., Warcoin, M., Rolland, E. et al. Results of a multigene panel testing approach targeting patients with suspected genetic predisposition to pancreatic ductal adenocarcinoma. Eur J Hum Genet (2026). https://doi.org/10.1038/s41431-026-02020-1

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