Titre :

Pédagogie à grande échelle en ACP

Auteur(s) :

Bancel, Léo-Paul [Auteur]
Masso, Vincent [Auteur]
Dessein, Anne-Frederique [Auteur]
Aubert, Sébastien [Auteur]
Leteurtre, Emmanuelle [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Coppin, Lucie [Auteur]
Odou, Marie-Françoise [Auteur]
Cao, Christine Do [Auteur]
Cardot-Bauters, Catherine [Auteur]
Pigny, Pascal [Auteur]

Titre de la revue :

Annales de Pathologie

Pagination :

144-150

Éditeur :

Elsevier Masson

Date de publication :

2019-04

ISSN :

0242-6498

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Abstract 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 ...
Lire la suite >Abstract 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

Vulgarisation :

Non

Collections :

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

Source :

Harvested from HAL