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Detection of relevant pharmacogenetic information through exome sequencing in oncology

    Simon Verdez

    *Author for correspondence: Tel.: +33 380 293 238;

    E-mail Address: simon.verdez@chu-dijon.fr

    UMR1231 GAD, Inserm – Université Bourgogne-Franche Comté, Dijon, France

    Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, 21000, France

    ,
    Juliette Albuisson

    Platform of Transfer in Cancer Biology, Georges François Leclerc Cancer Center – UNICANCER, Dijon, 21000, France

    Genomic & Immunotherapy Medical Institute, Dijon, 21000, France

    ,
    Yannis Duffourd

    UMR1231 GAD, Inserm – Université Bourgogne-Franche Comté, Dijon, France

    Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, 21000, France

    ,
    Romain Boidot

    Platform of Transfer in Cancer Biology, Georges François Leclerc Cancer Center – UNICANCER, Dijon, 21000, France

    Genomic & Immunotherapy Medical Institute, Dijon, 21000, France

    Department of Tumour Biology & Pathology, Georges François Leclerc Cancer Center – UNICANCER, Dijon, 21000, France

    ,
    Manon Reda

    Platform of Transfer in Cancer Biology, Georges François Leclerc Cancer Center – UNICANCER, Dijon, 21000, France

    Department of Tumour Biology & Pathology, Georges François Leclerc Cancer Center – UNICANCER, Dijon, 21000, France

    Department of Medical Oncology, Georges François Leclerc Cancer Center – UNICANCER, 1 rue Professeur Marion, Dijon, 21000, France

    ,
    Christel Thauvin-Robinet

    Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, 21000, France

    Genomic & Immunotherapy Medical Institute, Dijon, 21000, France

    Centre de Référence Maladies Rares “Anomalies du Développement et Syndromes Malformatifs”, Centre de Génétique, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, 21000, France

    ,
    Jean-David Fumet

    Department of Medical Oncology, Georges François Leclerc Cancer Center – UNICANCER, 1 rue Professeur Marion, Dijon, 21000, France

    ,
    Sylvain Ladoire

    Department of Medical Oncology, Georges François Leclerc Cancer Center – UNICANCER, 1 rue Professeur Marion, Dijon, 21000, France

    ,
    Sophie Nambot

    Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, 21000, France

    Centre de Référence Maladies Rares “Anomalies du Développement et Syndromes Malformatifs”, Centre de Génétique, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, 21000, France

    ,
    Patrick Callier

    UMR1231 GAD, Inserm – Université Bourgogne-Franche Comté, Dijon, France

    Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, 21000, France

    ,
    Laurence Faivre

    Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, 21000, France

    Genomic & Immunotherapy Medical Institute, Dijon, 21000, France

    Centre de Référence Maladies Rares “Anomalies du Développement et Syndromes Malformatifs”, Centre de Génétique, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, 21000, France

    ,
    François Ghiringhelli

    Platform of Transfer in Cancer Biology, Georges François Leclerc Cancer Center – UNICANCER, Dijon, 21000, France

    Genomic & Immunotherapy Medical Institute, Dijon, 21000, France

    Department of Tumour Biology & Pathology, Georges François Leclerc Cancer Center – UNICANCER, Dijon, 21000, France

    Department of Medical Oncology, Georges François Leclerc Cancer Center – UNICANCER, 1 rue Professeur Marion, Dijon, 21000, France

    &
    Nicolas Picard

    Inserm U1248, Service de Pharmacologie et Toxicologie, Université de Limoges, CHU de Limoges, Limoges, 87000, France

    Published Online:https://doi.org/10.2217/pgs-2022-0085

    Background: Germline sequencing of individual genomes can detect alleles responsible for adverse drug reactions (ADRs) in relation to chemotherapy, targeted agents, antiemetics or pain treatment. Materials & methods: To evaluate the interest of such pharmacogenetic information, the authors retrospectively analyzed genes known to have an impact on cancer therapy in a cohort of 445 solid cancers patients. Results: Six patients treated with 5-fluorouracil carrying one DPYD variant classified as 1A showed decreased drug mean clearance (p = 0.01). Regarding CYP2D6, all patients (n = 5) with predicted CYP2D6 poor or ultra-rapid metabolizer status experienced adverse drug reactions related to opioid therapy. Conclusion: Genomic germline sequencing performed for theragnostic issues in patients with a solid tumor, can provide relevant information about common pharmacogenetic alleles.

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