MET mutations are associated with aggressive and radioresistant brain metastatic non-small-cell lung cancer.

The onset of brain lesions resulting from non-small-cell lung cancer (NSCLC) is associated with a poor prognosis, with only 5% of patients surviving beyond the first year after diagnosis. 1 Only a minority of carefully selected patients can be recom-mended for surgical resection of brain metastases. 2 Palliative brain radiotherapy (BRT) could be efficacious in improving symptoms and quality of life. that inappropri-ate execution of the MET-driven “invasive growth” program is implicated in the metastatic process and that MET overexpres-sion promotes radiation-induced molecular status in se-ries of surgical samples from NSCLC, along with the corresponding brain metastases, in order to decipher the role of MET in predicting patients’ outcomes and radiotherapy responsiveness.Atotalof68NSCLC samples and their matched brain metastases were retrieved from consecutive cohorts from the archives of the pathology divisions of the University of at the Molinette of and of The study received ethical approval from local institutional review boards. Each sample was independently reviewed by 2 dedicated pathol-ogists (R.S. and P.C.), who confirmed all diagnoses according to the current World Health Organization classification. 6 We analyzed the entire coding sequence of MET , together with gene am-plification by fluorescence in situ hybridization analysis, as already described. 7 Age, gender, and radiotherapy of primary tumor and brain metastases, histotypes, and survival were ascertained for each case. Descriptive statistics were produced for demographic, clinical, and laboratory characteristics of cases. Cox regression was used to determine the association of patients’ characteristics with survival following diagnosis of brain metastases. progression; Kirsten rat sarcoma viral oncogene homolog. All the MET mutations were found clustered either in the juxtamembrane or in the extracellular semaphorin domain of the receptor. Both the T1010I and the E168D changes are already established somatic mutations, previously reported in both non-small- and small-cell lung cancers, displaying documented tumorigenic potential. None of the MET -mutated patients underwent chemotherapy after surgical removal of both primary and secondary lesions.