General information
The SALSA MLPA Probemix P308 MET is a research use only (RUO) assay for the detection of deletions or duplications in the MET, PTEN and LRRK2 genes.
The receptor tyrosine kinase MET (also known as hepatocyte growth factor receptor (HGFR) is frequently amplified in human cancers. Amplification results in high cell surface densities and constitutive activation of HGFR even in the absence of growth factor stimulation by its endogenous ligand, hepatocyte growth factor (HGF). MET gene is essential for survival and long-distance migration of epithelial and myogenic precursors during embryogenesis. Cancer cells hijack this biological process for invasion and metastasis. Multiple mechanisms can lead to aberrant MET activation, which occurs in many types of cancers.
MET gene amplifications leading to constitutive activation of the MET receptor are detected in a wide range of tumour types e.g. brain tumours, gastric cancer and lung tumours (Peters and Adjei 2012). Patients with papillary renal carcinomas carry both germline and somatic point mutations in MET (Schmidt et al. 1997; Schmidt et al. 1999). The amplification of leucine-rich repeat kinase-2 (LRRK2) is required for oncogenic MET signalling in papillary renal and in thyroid carcinomas and acts downstream of MET activation (Looyenga et al. 2011). Loss of tumour suppressor protein PTEN together with amplification of MET can be an alternative mechanism for primary resistance for tyrosine kinase inhibitors (EGFR-TKIs) (Engelman et al. 2007; Sos et al. 2009).

This SALSA MLPA probemix is not CE/FDA registered for use in diagnostic procedures. Purchase of this product includes a limited license for research purposes.

Probemix content
The SALSA MLPA Probemix P308-B3 MET contains 48 MLPA probes with amplification products between 130 and 493 nucleotides (nt). This includes 23 probes for the MET gene and three flanking probes for MET gene. This probemix also includes four probes for PTEN gene and four probes for LRRK2 gene. In addition, 14 reference probes are included detecting autosomal chromosomal locations, which are relatively copy number stable regions in various cancer types. The identity of the genes detected by the reference probes is available in Table 3. Complete probe sequences are available online (www.mrcholland.com).
This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at www.mrcholland.com.