MET oncogene is located on the chromosomal region 7q31 and encodes the receptor of hepatocytes growth factor (HGF) with tyrosine kinase activity. Two isoforms have been described for this gene. The resulting protein consists of two subunits, which arise from post-translational splicing. In adults, the MET receptor expression is limited to stem and progenitor cells, and is necessary for wound healing and regeneration of hepatocytes. Germinal mutations of MET gene have been found in patients with various types of cancers, such as papillary renal cell carcinoma. Mutations of MET gene are associated with a poor prognosis because they trigger tumor growth, angiogenesis and metastases.

Examination

We perform examination of the entire coding sequence (21 exons), including exon-intron connections of the MET gene. For the purpose of this examination, we use PCR amplification of given sections and direct sequencing.

MET gene mutations were found in 22% of cases of familial renal papillary carcinoma (pRCC) of type I and in 13% of sporadic cancers pRCC of type I (1). Numerous variations of the MET gene were found in 46% of pRCC of type II and in 81% of type I. The sequencing of the coding sequence and exon-intron connections covers 93% of known mutations of the MET gene.

Analytical sensitivity and specificity of sequencing: 99 %.

Limitations:

Mutations deep in the introns and regulatory sequences are not captured. Deletions and duplications will not be captured. Rare polymorphisms in place of primers settlement may cause a diagnostic error.

In the case of analysis of somatic mutations by sequencing, if the altered cell line is not represented at least by 20%, the mutations are not detected.

References

  1. Chen JD, Kearns S, Porter T, Richards FM, Maher ER, Teh BT. MET mutation andfamilial gastric cancer. J Med Genet. 2001 Aug;38(8):E26. PubMed PMID: 11483642; PubMed Central PMCID: PMC1734910.
  2. Stella GM, Benvenuti S, Gramaglia D, Scarpa A, Tomezzoli A, Cassoni P, SenettaR, Venesio T, Pozzi E, Bardelli A, Comoglio PM. MET mutations in cancers of unknown primary origin (CUPs). Hum Mutat. 2011 Jan;32(1):44-50. doi: 10.1002/humu.21374. Epub 2010 Nov 9. PubMed PMID: 20949619.
  3. Hanna JA, Bordeaux J, Rimm DL, Agarwal S. The function, proteolytic processing, and histopathology of Met in cancer. Adv Cancer Res. 2009;103:1-23. Review. PubMed PMID: 19854350.
  4. Albiges L, Guegan J, Le Formal A, Verkarre V, Rioux-Leclercq N, Sibony M, Bernhard JC, Camparo P, Merabet Z, Molinie V, Allory Y, Orear C, Couve S, Gad S, Patard JJ, Escudier B. MET is a potential target across all Papillary Renal Cell Carcinomas. Result from a large molecular study of pRCC with CGHa and matching Gene Expression array. Clin Cancer Res. 2014 Mar 21. [Epub ahead of print] PubMed PMID: 24658158.