Our analysis of publicly available datasets revealed that PTEN is frequently mutated in NSCLC, ranging from transcriptional downregulation to genetic loss, and frequently co-occur with gain of function mutations in the oncogene KRAS and loss of function mutations in the tumor suppressor TP53. PTEN gene dosage is a direct prognostic marker for therapy outcome and patient survival, as already a reduction in gene expression negatively correlated with patient survival and ionizing radiation therapy success for both NSCLC entities, adenocarcinoma and squamous cell carcinoma. Here, TP53 is linked to squamous cell carcinoma.