Titre :

Serum Succinate/Fumarate Ratio in Patients With Paraganglioma/Pheochromocytoma Attending an Endocrine Oncogenetic Unit

Auteur(s) :

Bancel, Léo-Paul [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Masso, Vincent [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Dessein, Anne-Frederique [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Aubert, Sébastien [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Leteurtre, Emmanuelle [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Service de pathologie [CHU Lille]
Coppin, Lucie [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Odou, Marie-Françoise [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Cao, Christine Do [Auteur]
Cardot-Bauters, Catherine [Auteur]
Service Endocrinologie, diabétologie, maladies métaboliques et nutrition [LILLE - Endocrino]
Pigny, Pascal [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]

Titre de la revue :

Journal of Clinical Endocrinology and Metabolism

Pagination :

2343-2352

Éditeur :

Endocrine Society

Date de publication :

2023-09-18

ISSN :

0021-972X

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Context Pheochromocytomas and paragangliomas (PPGLs) with SDHx pathogenic variants (PVs) are characterized by a higher intratissular succinate/fumarate ratio (RS/F) than non-SDHx–mutated ones. Also, an increase in serum ...
Lire la suite >Context Pheochromocytomas and paragangliomas (PPGLs) with SDHx pathogenic variants (PVs) are characterized by a higher intratissular succinate/fumarate ratio (RS/F) than non-SDHx–mutated ones. Also, an increase in serum succinate levels has been reported in patients with germline SDHB or SDHD PV. Objective To assess whether measurement of serum succinate, fumarate levels, and RS/F might aid identification of an SDHx germline PV/likely pathogenic variant (LPV) in patients with PPGL or in asymptomatic relatives; and to guide identification of a PV/LPV among the variants of unknown significance (VUS) identified in SDHx by next-generation sequencing. Methods This prospective monocentric study included 93 patients attending an endocrine oncogenetic unit for genetic testing. Succinate and fumarate were measured in serum by gas chromatography coupled to mass spectrometry. The RS/F was calculated to assess SDH enzymatic function. Diagnostic performance was assessed by receiver operating characteristic analysis. Results RS/F had a higher discriminant power than succinate alone to identify an SDHx PV/LPV in patients with PPGL. However, SDHD PVs/LPVs are frequently missed. Only RS/F differed between asymptomatic SDHB/SDHD PV/LPV carriers and SDHB/SDHD-linked patients with PPGL. Finally RS/F could be helpful to easily evaluate the functional impact of VUS in SDHx. Conclusion Measurement of serum RS/F in patients with PPGL and in asymptomatic relatives is a valuable initial workup tool to detect those carrying a germline PV/LPV in SDHx. Its discriminative power is equal or superior to those of succinate measured alone. SDHD PVs/LPVs are less frequently identified by these biochemical tools. Use of RS/F for SDHx VUS reclassification needs to be evaluated further.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Collections :

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

Source :

Harvested from HAL