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
- 30 June 2014
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 20 (13), 3411-3421
- https://doi.org/10.1158/1078-0432.ccr-13-2173
Abstract
International audiencePURPOSE: 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 \textgreater70%. 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. 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 statusKeywords
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This publication has 41 references indexed in Scilit:
- Initial Clinical Sensitivity and Acquired Resistance to MET Inhibition in MET-Mutated Papillary Renal Cell CarcinomaJournal of Clinical Oncology, 2013
- c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinomaAnnals of Oncology, 2013
- Type II papillary histology predicts poor outcome in patients with renal cell carcinoma and vena cava thrombusBJU International, 2012
- Correlation between MET Gene Copy Number by Silver In Situ Hybridization and Protein Expression by Immunohistochemistry in Non-small Cell Lung CancerJournal of Thoracic Oncology, 2012
- Genetic Activation of the MET Pathway and Prognosis of Patients With High-Risk, Radically Resected Gastric CancerJournal of Clinical Oncology, 2011
- MET Amplification Identifies a Small and Aggressive Subgroup of Esophagogastric Adenocarcinoma With Evidence of Responsiveness to CrizotinibJournal of Clinical Oncology, 2011
- An overview of the c-MET signaling pathwayTherapeutic Advances in Medical Oncology, 2011
- Chromosomal amplification of leucine-rich repeat kinase-2 (LRRK2) is required for oncogenic MET signaling in papillary renal and thyroid carcinomasProceedings of the National Academy of Sciences of the United States of America, 2011
- 2009 update on the classification of renal epithelial tumors in adultsInternational Journal of Urology, 2009
- Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray ExperimentsStatistical Applications in Genetics and Molecular Biology, 2004