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MET
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Interpretation 2310
Tier 3
MET
Variants
MET M362T
Primary Sites
Thyroid
Tumor Types
Carcinoma
Interpretation

The Mesenchymal Epithelial Transition (MET) proto-oncogene encodes the MET receptor tyrosine kinase, also called c-MET or hepatocyte growth factor (HGF) receptor. MET is a ubiquitously expressed cell surface receptor that leads to the activation of several downstream intracellular pathways which promote cellular growth and proliferation, motility, migration and angiogenesis. Dysregulation of MET via gene amplification, germline or somatic mutations or receptor overexpression has been observed in a variety of epithelial cancers, including breast prostate cancer, non-small cell lung cancer, renal papillary carcinoma, hepatocellular and gastric carcinomas. Genetic alterations in MET have been identified in 0.4% of thyroid carcinomas. The prognostic and predictive significance of MET mutations in thyroid cancer is not clear and correlation with other clinical and laboratory findings is necessary. M362T has been identified in the scientific literature, but has not been biochemically characterized and therefore, its effect on protein function is unknown. This variant is reported as a benign/likely benign germline variant in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/93565).

Citations
  1. Sakai K, Aoki S, Matsumoto K. Hepatocyte growth factor and Met in drug
  2. discovery. J Biochem. 2015 May;157(5):271-84. doi: 10.1093/jb/mvv027. Epub 2015 Mar 13. Review. PubMed PMID: 25770121.
  3. Lengyel E, Prechtel D, Resau JH, Gauger K, Welk A, Lindemann K, Salanti G, Richter T, Knudsen B, Vande Woude GF, Harbeck N. C-Met overexpression in node-positive breast cancer identifies patients with poor clinical outcome independent of Her2/neu. Int J Cancer. 2005 Feb 10;113(4):678-82.
  4. Tsao MS, Liu N, Chen JR, Pappas J, Ho J, To C, Viallet J, Park M, Zhu H. Differential expression of Met/hepatocyte growth factor receptor in subtypes of non-small cell lung cancers. Lung Cancer. 1998 Apr;20(1):1-16.
  5. Fay AP, Signoretti S, Choueiri TK. MET as a target in papillary renal cell carcinoma. Clin Cancer Res. 2014 Jul 1;20(13):3361-3.
  6. Comprehensive TCGA PanCanAtlas (https://gdc.cancer.gov/about data/publications/pancanatlas)
  7. Volckmar AL, Leichsenring J, Flechtenmacher C, Pfarr N, Siebolts U, Kirchner
  8. M, Budczies J, Bockmayr M, Ridinger K, Lorenz K, Herpel E, Noske A, Weichert W,Klauschen F, Schirmacher P, Penzel R, Endris V, Stenzinger A. Tubular, lactating,and ductal adenomas are devoid of MED12 Exon2 mutations, and ductal adenomas show recurrent mutations in GNAS and the PI3K-AKT pathway. Genes Chromosomes Cancer.2017 Jan;56(1):11-17.
  9. Costa V, et al. New somatic mutations and WNK1-B4GALNT3 gene fusion in papillary thyroid carcinoma. Oncotarget 2015;6(13):11242-11251
  10. National Center for Biotechnology Information. ClinVar; Variation ID 93565, https://preview.ncbi.nlm.nih.gov/clinvar/variation/93565.
Last updated: 2019-01-22 18:42:32 UTC
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