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

作者：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; Couve Sophie; Gad Sophie; Patard Jean Jacques; Escudier Bernard

来源：Clinical Cancer Research, 2014, 20(13): 3411-3421.

DOI：10.1158/1078-0432.CCR-13-2173

Purpose: 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. %26lt;br%26gt;Experimental Design: We collected 220 frozen samples of sporadic pRCC through the French RCC Network and quality controlled for percentage of malignant cells %26gt;70%. Gene expression was assessed on 98 pRCC using human whole-genome Agilent 8 x 60K arrays. Copy number alterations were analyzed using Agilent Human 2 x 400K and 4 x 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. %26lt;br%26gt;Results: 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. %26lt;br%26gt;Conclusion: 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.

• 出版日期2014-7-1