Fiche publication
Date publication
décembre 2021
Journal
Human mutation
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LIMACHER Jean-Marc
,
Dr MAUGARD Christine
Tous les auteurs :
Sebai M, Tulasne D, Caputo SM, Verkarre V, Fernandes M, Reinhart F, Adams S, Maugard C, Caron O, Guillaud-Bataille M, Berthet P, Bignon YJ, Bressac-de Paillerets B, Burnichon N, Chiesa J, Giraud S, Lejeune S, Limacher JM, de Pauw A, Stoppa-Lyonnet D, Zattara-Cannoni H, Deveaux S, Lidereau R, Richard S, Rouleau E
Lien Pubmed
Résumé
Hereditary papillary renal cell carcinoma (HPRC) is a rare inherited renal cancer syndrome characterized by bilateral and multifocal papillary type 1 renal tumors (PRCC1). Activating germline pathogenic variants of MET gene were identified in HPRC families. We reviewed the medical and molecular records of a large French series of 158 patients screened for MET oncogenic variants. MET pathogenic and likely pathogenic variants rate was 12.4% with 40.6% among patients with familial PRCC1 and 5% among patients with sporadic PRCC1. The phenotype in cases with MET pathogenic and likely pathogenic variants was characteristic: PRCC1 tumors were mainly bilateral (84.3%) and multifocal (87.5%). Histologically, six out of seven patients with MET pathogenic variant harboured biphasic squamoid alveolar PRCC. Genetic screening identified one novel pathogenic variant MET c.3389T>C, p.(Leu1130Ser) and three novel likely pathogenic variants: MET c.3257A>T, p.(His1086Leu); MET c.3305T>C, p.(Ile1102Thr) and MET c.3373T>G, p.(Cys1125Gly). Functional assay confirmed their oncogenic effect as they induced an abnormal focus formation. The genotype-phenotype correlation between MET pathogenic variants and PRCC1 presentation should encourage to widen the screening, especially toward non-familial PRCC1. This precise phenotype also constitutes a strong argument for the classification of novel missense variants within the tyrosine kinase domain when functional assays aren't accessible. This article is protected by copyright. All rights reserved.
Mots clés
Biphasic squamoid alveolar papillary renal cell carcinoma, Genotype-Phenotype Correlation, Germline Mutation, Mutation Rate, Papillary renal cell carcinoma
Référence
Hum Mutat. 2021 Dec 9;:
