MET

Pathology

 MET germline activating mutations in:

• familial papillary renal carcinoma (MIM.605074)
• familial colorectal cancer (21970370)

 MET somatic activating mutations in:

• sporadic papillary renal carcinoma (MIM.605074)
• childhood type hepatocellular carcinoma (MIM.114550)

 MET amplification in :

• MET-amplified gastric carcinoma (26404902)

 MET overexpression in :

• MET-amplified gastric carcinoma (26404902)

Targeted therapy

Several c-MET targeting inhibitory molecules have already shown promising results in the treatment of patients with Non-small Cell Lung Cancer (NSCLC). Combination of EGFR- and c-MET-specific molecules may overcome EGFR tyrosine kinase inhibitor (TKI) resistance.

Neither expression of c-MET, nor the gene amplification status might be the best way to select patients for MET targeting therapies, since no correlation with the activation status of MET was observed. (26215852)

Open references

 Improved diagnostics targeting c-MET in non-small cell lung cancer: expression, amplification and activation? Watermann I, Schmitt B, Stellmacher F, Müller J, Gaber R, Kugler Ch, Reinmuth N, Huber RM, Thomas M, Zabel P, Rabe KF, Jonigk D, Warth A, Vollmer E, Reck M, Goldmann T. Diagn Pathol. 2015 Jul 28;10:130. doi : 10.1186/s13000-015-0362-5 PMID: 26215852 (Free)

References

 Activating mutation in MET oncogene in familial colorectal cancer. 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. BMC Cancer. 2011 Oct 4;11:424. PMID: 21970370

 Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms. Hansel DE, Rahman A, House M, Ashfaq R, Berg K, Yeo CJ, Maitra A. Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6152-8. PMID: 15448002

 Tsuda M, Davis IJ, Argani P, Shukla N, McGill GG, Nagai M, Saito T, Lae M, Fisher DE, Ladanyi M. TFE3 fusions activate MET signaling by transcriptional up-regulation, defining another class of tumors as candidates for therapeutic MET inhibition. Cancer Res. 2007 Feb 1;67(3):919-29. PMID: 17283122

 Chen Y, Takita J, Mizuguchi M, Tanaka K, Ida K, Koh K, Igarashi T, Hanada R, Tanaka Y, Park MJ, Hayashi Y. Mutation and expression analyses of the MET and CDKN2A genes in rhabdomyosarcoma with emphasis on MET overexpression. Genes Chromosomes Cancer. 2007 Apr;46(4):348-58. PMID: 17243166

 Corso S, Comoglio PM, Giordano S. Cancer therapy: can the challenge be MET? Trends Mol Med. 2005 Jun;11(6):284-92. PMID: 15949770

 Dharmawardana PG, Giubellino A, Bottaro DP. Hereditary papillary renal carcinoma type I. Curr Mol Med. 2004 Dec;4(8):855-68. PMID: 15579033

 Rosario M, Birchmeier W. How to make tubes: signaling by the Met receptor tyrosine kinase. Trends Cell Biol. 2003 Jun;13(6):328-35. PMID: 12791299