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MET
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Interpretation 2360
Tier 3
MET
Variants
MET T1010I
Primary Sites
Colon
Tumor Types
Fibromatosis
Interpretation

MET is a receptor tyrosine kinase that has been shown to frequently be altered (mutation or amplification) in various cancers, leading to overexpression. The p.T1010I mutation, in the cytoplasmic juxtamembrane domain of MET has been shown to increase growth factor independent proliferation and motility in vitro in tumor cell lines in some studies. However, the functional effect of T1010I is conflicting, as it has been reported both to have phosphorylation level and transforming capacity similar to wild-type Met protein (PMID: 20670955) This variant has also been reported as a germline variant present in less than 1% of the general population. Its role in tumor development and progression continues to be studied. Due to conflicting reports of pathogenicity, this variant best characterized as a variant of uncertain significance (VUS) (https://www.ncbi.nlm.nih.gov/clinvar/variation/41624/).

Citations
  1. Neklason DW, Done MW, Sargent NR, Schwartz AG, Anton-Culver H, Griffin CA, Ahnen DJ, Schildkraut JM, Tomlinson GE, Strong LC, Miller AR, Stopfer JE, Burt RW. Activating mutation in MET oncogene in familial colorectal cancer. BMC Cancer. 2011 Oct 4;11:424. doi: 10.1186/1471-2407-11-424. PubMed PMID: 21970370
  2. Ma PC, Jagadeeswaran R, Jagadeesh S, Tretiakova MS, Nallasura V, Fox EA, Hansen M, Schaefer E, Naoki K, Lader A, Richards W, Sugarbaker D, Husain AN, Christensen JG, Salgia R. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res. 2005 Feb 15;65(4):1479-88. PubMed PMID: 15735036.
  3. Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, Griffin JD, Johnson BE, Salgia R. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res. 2003 Oct 1;63(19):6272-81. PubMed PMID: 14559814
  4. Jagadeeswaran R, Ma PC, Seiwert TY, Jagadeeswaran S, Zumba O, Nallasura V, Ahmed S, Filiberti R, Paganuzzi M, Puntoni R, Kratzke RA, Gordon GJ, Sugarbaker DJ, Bueno R, Janamanchi V, Bindokas VP, Kindler HL, Salgia R. Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma. Cancer Res. 2006 Jan 1;66(1):352-61. PubMed PMID: 16397249.
  5. Liu S, et al. Functional consequence of the MET-T1010I polymorphism in breast cancer. Oncotarget 2015;6(5). PubMedPMID: 25605252
  6. Tyner JW. MET receptor sequence variants R970C and T992I lack transforming capacity. Cancer Res 2010;70(15)6233-7. PubMed PMID: 20670955
Last updated: 2019-08-29 17:55:27 UTC
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