Title :

Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity

Author(s) :

Larrue, Romain [Auteur correspondant]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Fellah, Sandy [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Hennart, Benjamin [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Sabaouni, Naoual [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Boukrout, Nihad [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Van Der Hauwaert, Cynthia [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Delage, Clément [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Cheok, Meyling [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Perrais, Michaël [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Cauffiez, Christelle [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Allorge, Delphine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Pottier, Nicolas [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]

Journal title :

Pharmacogenomics Journal

Pages :

1

Publisher :

Nature Publishing Group

Publication date :

2024-01-12

ISSN :

1470-269X

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Variability in genes involved in drug pharmacokinetics or drug response can be responsible for suboptimal treatment efficacy or predispose to adverse drug reactions. In addition to common genetic variations, large-scale ...
Show more >Variability in genes involved in drug pharmacokinetics or drug response can be responsible for suboptimal treatment efficacy or predispose to adverse drug reactions. In addition to common genetic variations, large-scale sequencing studies have uncovered multiple rare genetic variants predicted to cause functional alterations in genes encoding proteins implicated in drug metabolism, transport and response. To understand the functional importance of rare genetic variants in DPYD , a pharmacogene whose alterations can cause severe toxicity in patients exposed to fluoropyrimidine-based regimens, massively parallel sequencing of the exonic regions and flanking splice junctions of the DPYD gene was performed in a series of nearly 3000 patients categorized according to pre-emptive DPD enzyme activity using the dihydrouracil/uracil ([UH 2 ]/[U]) plasma ratio as a surrogate marker of DPD activity. Our results underscore the importance of integrating next-generation sequencing-based pharmacogenomic interpretation into clinical decision making to minimize fluoropyrimidine-based chemotherapy toxicity without altering treatment efficacy.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL