Journal article
Novel mutations of the MET proto-oncogene in papillary renal carcinomas
Oncogene, Vol.18(14), pp.2343-2350
04/08/1999
DOI: 10.1038/sj.onc.1202547
PMID: 10327054
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.
Details
- Title: Subtitle
- Novel mutations of the MET proto-oncogene in papillary renal carcinomas
- Creators
- Laura Schmidt - Science Applications International CorporationKerstin Junker - SchillerNoboru Nakaigawa - Laboratory of Immunobiology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, USATracy Kinjerski - Science Applications International CorporationGregor Weirich - Laboratory of Immunobiology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, USAMaria Miller - National Cancer InstituteIrina Lubensky - National Institutes of HealthHartmut PH Neumann - Albert-Ludwigs-University, GermanyHiltrud Brauch - EppendorfJohann DeckerCathy Vocke - National Institutes of HealthJames A Brown - Grant Medical CenterRobert Jenkins - Mayo ClinicStephane Richard - Bicêtre HospitalUlf BergerheimBernard Gerrard - Science Applications International CorporationMichael Dean - National Cancer InstituteW Marston Linehan - National Institutes of HealthBerton Zbar - Laboratory of Immunobiology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, USA
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.18(14), pp.2343-2350
- DOI
- 10.1038/sj.onc.1202547
- PMID
- 10327054
- ISSN
- 0950-9232
- eISSN
- 1476-5594
- Language
- English
- Date published
- 04/08/1999
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Urology
- Record Identifier
- 9984320852102771
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