• Laurence Albiges, Justine Guegan, Audrey Le Formal, Virginie Verkarre, Nathalie Rioux-Leclercq, Mathilde Sibony, Jean-Christophe Bernhard, Philippe Camparo, Zahira Merabet, Vincent Molinie, Yves Allory, Cedric Orear, Sophie Couvé, Sophie Gad, Jean-Jacques Patard, and Bernard Escudier.
• Authors' Affiliations: Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France; INSERM U753, IGR, Villejuif, France; Laurence.albiges@gustaveroussy.fr.
• Clin Cancer Res. 2014 Jul 1; 20 (13): 3411-21.

PurposePapillary renal cell carcinomas (pRCC) are the most common nonclear cell RCC subtype. Germline mutations of the MET oncogene at 7q31 have been detected in patients with hereditary type I pRCC and in 13% of sporadic type I pRCC. Recent report of MET inhibition strengthened the role of c-Met inhibition across pRCC.Experimental DesignWe collected 220 frozen samples of sporadic pRCC through the French RCC Network and quality controlled for percentage of malignant cells >70%. Gene expression was assessed on 98 pRCC using human whole-genome Agilent 8 × 60K arrays. Copy number alterations were analyzed using Agilent Human 2 × 400K and 4× 180K array for type II pRCC and comparative genomic microarray analysis method for type I pRCC. MET gene sequencing was performed on type I pRCC.ResultsMET expression level was high across all pRCC. We identified copy number alterations (gain) in 46% of type II pRCC and in 81% of type I pRCC. Correlation between DNA copy number alterations and mRNA expression level was highly significant. Eleven somatic mutations of MET gene were identified amongst 51 type I pRCC (21.6%), including 4 new mutations. We validated LRRK2 cokinase as highly correlated to MET expression.ConclusionThe present report expands the role of MET activation as a potential target across all pRCC subtypes. These data support investigating MET inhibitors in pRCC in correlation with MET activation status.©2014 American Association for Cancer Research.

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