Journal
CLINICAL CANCER RESEARCH
Volume 20, Issue 13, Pages 3411-3421Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-13-2173
Keywords
-
Categories
Funding
- ARTuR grant
- University of Paris-Sud and Gustave Roussy Institute, Villejuif
Ask authors/readers for more resources
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. Experimental Design: 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 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. 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. 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. (C)2014 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available