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Sebai M, Tulasne D, Caputo SM, et al. Novel germline MET pathogenic variants in French patients with papillary renal cell carcinomas type I. Hum Mutat. 2021;doi: 10.1002/humu.24313.
Sebai, M., Tulasne, D., Caputo, S. M., Verkarre, V., Fernandes, M., Reinhart, F., Adams, S., Maugard, C., Caron, O., Guillaud-Bataille, M., Berthet, P., Bignon, Y. J., Bressac-de Paillerets, B., Burnichon, N., Chiesa, J., Giraud, S., Lejeune, S., Limacher, J. M., de Pauw, A., Stoppa-Lyonnet, D., Zattara-Cannoni, H., Deveaux, S., Lidereau, R., Richard, S., & Rouleau, E. (2021). Novel germline MET pathogenic variants in French patients with papillary renal cell carcinomas type I. Human mutation, . https://doi.org/10.1002/humu.24313
Sebai, Molka, et al. "Novel germline MET pathogenic variants in French patients with papillary renal cell carcinomas type I." Human mutation vol. (2021). doi: https://doi.org/10.1002/humu.24313
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. Novel germline MET pathogenic variants in French patients with papillary renal cell carcinomas type I. Hum Mutat. 2021 Dec 09; doi: 10.1002/humu.24313. Epub 2021 Dec 09. PMID: 34882875.
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Hum Mutat. 2021 Dec 09; doi: 10.1002/humu.24313. Epub 2021 Dec 09.

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

Human mutation

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

Affiliations

  1. Department of Medical Biology and Pathology, Cancer Genetics Laboratory, Gustave Roussy, 94800, Villejuif, France.
  2. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000, Lille, France.
  3. Department of Genetics, Institut Curie, 75005, Paris, France.
  4. Paris Sciences Lettres Research University, 75005, Paris, France.
  5. Department of Pathology, Georges Pompidou European Hospital, Assistance Publique Hôpitaux de Paris, 75015, Paris, France.
  6. French National Network for Rare Cancers in Adults PREDIR labelled by INCa, AP-HP, Hôpital Bicêtre, 94270, Le Kremlin-Bicêtre, France.
  7. Department of molecular oncogenetics, Hôpitaux Universitaires de Strasbourg, 67091, Strasbourg, France.
  8. Department of Medical Oncogenetics, Gustave Roussy, 94800, Villejuif, France.
  9. Oncogenetics Department, Centre François Baclesse, 14000, Caen, France.
  10. Oncogenetics Department, Centre Jean-Perrin, BP 392, 63011, Clermont-Ferrand, France.
  11. Université de Paris, AP-HP, Hôpital Européen Georges Pompidou, Genetics department, Paris, France.
  12. Department of Cytogenetics, Nimes University Hospital, 30029, Nîmes, France.
  13. Genetics Department, Hospices Civils de LYON (HCL), 69002, Lyon, France.
  14. Department of genetics, CHRU Lille, 59000, Lille, France.
  15. Genetics Department, Hôpitaux civils de Colmar, 68024, COLMAR, France.
  16. INSERM U830, Institut Curie Paris, 75505, Paris, France.
  17. Paris-University, 75006, Paris, France.
  18. Department of Genetics, Hôpital de la Timone Enfants, 13005, Marseille, France.
  19. EPHE, PSL University, UMR 9019 CNRS, Paris-Saclay University, Gustave Roussy, 94800, Villejuif, France.

PMID: 34882875 DOI: 10.1002/humu.24313

Abstract

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.

This article is protected by copyright. All rights reserved.

Keywords: Biphasic squamoid alveolar papillary renal cell carcinoma; Genotype-Phenotype Correlation; Germline Mutation; Mutation Rate; Papillary renal cell carcinoma

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