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MET is a potential target across all papillary renal cell carcinomas: result from a large molecular study of pRCC with CGH array and matching gene expression array.

Albiges, Laurence; Guegan, Justine; Le Formal, Audrey; Verkarre, Virginie; Rioux-Leclercq, Nathalie; Sibony, Mathilde; Bernhard, Jean-Christophe; Camparo, Philippe; Merabet, Zahira; Molinie, Vincent; Allory, Yves; Orear, Cedric; Couvé, Sophie; Gad, Sophie; Patard, Jean-Jacques; Escudier, Bernard.
Clin Cancer Res; 20(13): 3411-21, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24658158


Papillary 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


We 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.


MET 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.


The 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.
Selo DaSilva