@article{dc3cbaa256ff43ca850021ea1eb59594,
title = "Novel mutations of the MET proto-oncogene in papillary renal carcinomas",
abstract = "Hereditary papillary renal carcinoma (HPRC) is characterized by multiple, bilateral papillary renal carcinomas. Previously, we demonstrated missense mutations in the tyrosine kinase domain of the MET proto-oncogene in HPRC and a subset of sporadic papillary renal carcinomas. In this study, we screened a large panel of sporadic papillary renal carcinomas and various solid tumors for mutations in the MET protooncogene. Summarizing these and previous results, mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary renal carcinomas but not in other solid tumors. We detected five novel missense mutations; three of five mutations were located in the ATP-binding region of the tyrosine kinase domain of MET. One novel mutation in MET, V1110I, was located at a codon homologous to an activating mutation in the c-erbB proto-oncogene. These mutations caused constitutive phosphorylation of MET when transfected into NIH3T3 cells. Molecular modeling studies suggest that these activating mutations interfere with the intrasteric mechanism of tyrosine kinase autoinhibition and facilitate transition to the active form of the MET kinase. The low frequency of MET mutations in noninherited papillary renal carcinomas (PRC) suggests that non-inherited PRC may develop by a different mechanism than hereditary papillary renal carcinoma.",
keywords = "MET protooncogene mutations, Papillary renal carcinoma, Receptor tyrosine kinase",
author = "Laura Schmidt and Kerstin Junker and Noboru Nakaigawa and Tracy Kinjerski and Gregor Weirich and Maria Miller and Irina Lubensky and Neumann, {Hartmut Ph} and Hiltrud Brauch and Johann Decker and Cathy Vocke and Brown, {James A.} and Robert Jenkins and Stephane Richard and Ulf Bergerheim and Bernard Gerrard and Michael Dean and Linehan, {W. Marston} and Berton Zbar",
note = "Funding Information: We thank Drs Scott Kern, Bert Vogelstein, Marcel Mannens, Marius Skudlinski, Gloria Niehans, Holger Moch, Webster Cavanee, Sandra Bigner, Burt Feuerstein, McClellan Walther, Kimberly Newsom Johnson/Vanderbilt Tissue Procurement Lab, Sharon Howard/Fox Chase Cancer Center, Paolo Radice, Michael Hughson, Masa-hiro Yao, Suzanne Topalian, Virginia LiVolsi, and Bruce Weintraub for providing tumor samples or DNA for mutation analysis. In addition we thank Dr Gerd Riedasch, Department of Urology, Rupert-Karls-University, Heidelberg, Germany for clinical evaluation of PRC patients and Dr JA Brown, Mayo Clinic (Rochester, MN, USA) for karyotypic and histologic analyses of metanephric adenomas. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-56000 and under contract with ABL (MM). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The publisher or recipient acknowledges right of the US Government to retain a nonexclusive, royalty-free license in and to any copyright covering the article.",
year = "1999",
month = apr,
day = "8",
doi = "10.1038/sj.onc.1202547",
language = "English (US)",
volume = "18",
pages = "2343--2350",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "14",
}