Details

Autor(en) / Beteiligte

• Sebai, Molka
• Tulasne, David
• Caputo, Sandrine M.
• Verkarre, Virginie
• Fernandes, Marie
• Guérin, Célia
• Reinhart, Fanny
• Adams, Séverine
• Maugard, Christine
• Caron, Olivier
• Guillaud‐Bataille, Marine
• Berthet, Pascaline
• Bignon, Yves‐Jean
• Bressac‐de Paillerets, Brigitte
• Burnichon, Nelly
• Chiesa, Jean
• Giraud, Sophie
• Lejeune, Sophie
• Limacher, Jean‐Marc
• Pauw, Antoine
• Stoppa‐Lyonnet, Dominique
• Zattara‐Cannoni, Hélène
• Deveaux, Sophie
• Lidereau, Rosette
• Richard, Stéphane
• Rouleau, Etienne

Titel

Novel germline MET pathogenic variants in French patients with papillary renal cell carcinomas type I

Ist Teil von

• Human mutation, 2022-03, Vol.43 (3), p.316-327

Ort / Verlag

United States: Hindawi Limited

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 the 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 harbored 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 nonfamilial PRCC1. This precise phenotype also constitutes a strong argument for the classification of novel missense variants within the tyrosine kinase domain when functional assays are not accessible. Classification of new MET pathogenic variants in French patients with papillary renal cell carcinomas type I