If these results are further validated in a similar population, they could be incorporated into future prognostic instruments, potentially aiding the design of adjuvant clinical trials of MET inhibitors and management of renal-cell carcinoma.
Dysregulation of c-Met and hepatocyte growth factor have been observed in both clear cell and non-clear cell renal cell carcinomas (RCCs), although only papillary RCCs harbor activating mutations in the MET gene.
Germline mutations in the MET and fumarate hydratase (FH) genes lead to the development of type 1 and type 2 papillary RCCs, respectively, and such mutations of either the TSC1 or TSC2 gene increase the risk of RCC.
Likewise, papillary RCC has also been studied at the molecular level, which has shown a high level of mutations in the MET gene; early clinical data suggest the utility of MET targeted therapy.
Our results indicate that expression of the MET proto-oncogene above a critical threshold is required for the maintenance of the tumorigenic phenotype of at least some papillary renal cell carcinomas, but does not further increase during tumour progression.
Investigation of rare familial forms of renal cell carcinoma (RCC) has led to the identification of genes such as VHL and MET that are also implicated in the pathogenesis of sporadic RCC.
If these results are further validated in a similar population, they could be incorporated into future prognostic instruments, potentially aiding the design of adjuvant clinical trials of MET inhibitors and management of renal-cell carcinoma.
Germline mutations in the tyrosine-kinase domain of the MET proto-oncogene were found in patients suffering from the hereditary predisposition to develop multiple papillary renal-cell carcinomas (hereditary PRCC, HPRCC).
Mechanistic, preclinical, and early clinical data highlight c-Met / hepatocyte growth factor receptor as a promising target for RCC therapeutic agents.We have examined MET expression, frequency of MET gene copy gains and MET gene mutation in a large, hospital-based series of renal cell carcinomas with long-term follow-up information.Out of a total of 572 clear-cell RCC, only 17% were negative for MET expression whereas 32% showed high protein levels.
Studies of the hereditary form of renal cell carcinoma (RCC) associated with hereditary papillary renal carcinoma (HPRC) determined that the c-Met proto-oncogene on chromosome 7 is the gene for HPRC and for a number of sporadic papillary RCCs.
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.
Wilms' tumour and the WT-1 gene, renal cell carcinoma and the c-met receptor tyrosine kinase gene), some to be caused by mutations in genes expressed during normal development (e.g. renal cell carcinoma and the TSC-2 gene, renal cell carcinoma of the clear cell variety and the VHL gene).
C-Met protein levels were increased in 8 of 10 RCC tissue samples compared with their adjacent normal tissue and c-Met expression levels were positively associated with a high nuclear grade (P = 0.008) and pT stage (P = 0.002).