**3.4 MET and RET mutations**

The large variety of mutations in EMT: (mesenchymal epithelial transition factor) affects a range of cancers, including NSCLC. The MET gene codes for a tyrosinekinase receptor that plays role in developmental processes and wound healing. Hepatic growth factor/scatter factor (HGF/SF) and their splice isoforms NK1 and 2 are the only known ligands of the MET receptor. In cancer, abnormal MET activation triggers proliferation, angiogenesis, and metastasis. The MET pathways interfere with the key oncogenic pathways RAS, P13K, STAT3, and beta catenin. In general, mutations consist of duplications of mutant alleles, intronic splice site alterations, and mutations affecting the receptor downstream targets. In NSCLC BM, the majority of

*Non-Small Cell Lung Cancer Brain Metastasis: The Link between Molecular Mechanisms… DOI: http://dx.doi.org/10.5772/intechopen.106385*

MET mutations found at metastatic sites affect the extracellular SEMA: Semaphorin superfamily domain of the receptor [60–62]. Remarkably, mutations in MET occur more frequently in CNS metastasis from NSCLC than in their primary tumors. RET chromosomal rearrangements have been detected in 1–2% of all patients with NSCLC, particularly in patients with adenocarcinoma. The rearrangements are mutually exclusive with EGFR, ALK, or RAS mutations [63]. Importantly, NSCLC with RET rearrangement is associated with an increased risk of BMs [64].
