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MET
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Interpretation 2345
Tier 3
MET
Variants
MET N375K
Primary Sites
Soft Tissue
Tumor Types
Chondrosarcoma
Interpretation

MET is a member of the receptor tyrosine kinase and proto-oncogene playing a major role in tumor development and metastasis. Nonsynonymous mutations in the MET gene have been rarely described in sarcomas (<2%). The N375K variant has been reported as a somatic variant in two cases of NSCLC. It has been also reported in a single family with familial EGFR-mutant lung adenocarcinoma. This variant lies in the non-kinase domain of the protein. Further functional studies showed this mutation reduced the binding affinity of MET for its ligand, hepatocyte growth factor (HGF), damaging subsequent cellular processes including proliferation, motility and tumorigenicity. In ClinVar it is reported as a germline variant of unknown significance (https://preview.ncbi.nlm.nih.gov/clinvar/variation/572621/). The activity of MET inhibitors in tumors with non-kinase domain MET mutations is not yet known. The clinical significance of this mutation in this tumor is uncertain. Clinical correlation is recommended.

Citations
  1. Krishnaswamy et al. Ethnic Differences and Functional Analysis of MET Mutations in Lung Cancer.Clin Cancer Res 2009;15(18) September 15, 2009
  2. Monica Kong-Beltran et al. Somatic Mutations Lead to an Oncogenic Deletion of MET in Lung Cancer. Cancer Res 2006; 66(1): 283-9
  3. Zehir A, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 2017;23(6):703-713
  4. Takahashi Y, et al. Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis. Cancer Sci 2018;109(11):3634-3642
  5. Tode N, et al. Exome sequencing deciphers a germline MET mutation in familial epidermal growth factor receptor-mutant lung cancer. Cancer Sci 2017;108(6):1263-1270
  6. ClinVar. https://preview.ncbi.nlm.nih.gov/clinvar/variation/572621
  7. OncoKB. https://oncokb.org/gene/MET/N375K
Last updated: 2019-04-03 14:35:22 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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