title: Papillary renal cell carcinoma with a somatic mutation in MET in a patient with autosomal dominant polycystic kidney disease.
abstract: Autosomal-dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2 and is characterized by proliferation of renal tubular epithelium and progressive chronic kidney disease. Derangements in similar cellular signaling pathways occur in ADPKD and renal malignancies, although an association of these disorders has not been established. Herein, we present a case of papillary RCC (pRCC) incidentally discovered in a patient with ADPKD following bilateral native nephrectomy during renal transplantation. Whole exome sequencing of the pRCC found a somatic missense mutation in MET proto-oncogene, p.Val1110Ile, not present in kidney cyst epithelium or non-cystic tissue. RNA sequencing demonstrated increased mRNA expression of MET and pathway-related genes, but no significant copy number variation of MET was detected. Genetic analysis of PKD genes from peripheral blood lymphocytes and renal cyst epithelium identified a constitutional PKD1 germline mutation, p.Trp1582Ser, predicted to be pathogenic. Unique somatic mutations in PKD1 were also detected in 80% of the renal cysts analyzed, but not in the pRCC. These results suggest that, in this patient, the pRCC utilized a signaling pathway involving MET that was distinct from the pathogenesis of ADPKD. This is the first report of PKD1 mutations and a somatic mutation of the MET oncogene in a pRCC in ADPKD.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Wanying
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA; Department of Microbiology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Adrian Y
authors.initials: AY
authors.lastname: Tan
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY, USA; The Rogosin Institute, New York, NY, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Blumenfeld
authors.affiliation: The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Genyan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Alber
authors.initials: A
authors.lastname: Michaeel
authors.affiliation: Department of Microbiology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Tuo
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Salvatore
authors.affiliation: Department of Surgery, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Sandip
authors.initials: S
authors.lastname: Kapur
authors.affiliation: The Rogosin Institute, New York, NY, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Donahue
authors.affiliation: The Rogosin Institute, New York, NY, USA.
authors.forename: Warren O
authors.initials: WO
authors.lastname: Bobb
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: har2006@med.cornell.edu.
authors.forename: Hanna
authors.initials: H
authors.lastname: Rennert
mesh_terms: D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: ADPKD; MET; long-range PCR; next generation sequencing; pRCC