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Personalised cancer treatment depends on identification of therapeutically relevant biological subgroups of patients for assessing effect of treatment and to discover new therapeutic options. By analyses in heterogeneous patient populations, the effects may be lost in noise. Squamous cell carcinoma of the lung is a major killer worldwide. Despite recent advances, mortality is high and response to therapies varies greatly from patient to patient. Target search in biologically relevant subgroups may identify treatment options not so far discovered. A total of 198 patients undergoing surgery for squamous cell carcinomas of the lung were included in the study. The tumours were analysed for copy number alterations (n = 152) and gene expression from tumour (n = 188) and normal lung (n = 21), with both data levels present in 140 patients. We studied alterations in tumours harbouring mutations in  TP53  and in previously published gene expression subtypes. Genes with consistent alterations in both genomic levels were identified as putative biomarkers. Results were validated in TCGA. The most convincing biomarker in  TP53  mutated squamous cell carcinomas of the lung was  BIRC5  with amplification in 36% of mutated samples, 5% in wild‐type samples and a 17%‐fold change of expression between  TP53  mutated tumours and normal lung tissue.  BIRC5  was significantly altered in the classical and primitive subtypes. We suggest  BIRC5  as a putative predictive biomarker and putative druggable target in squamous cell lung carcinomas harbouring  TP53  mutation or classified as classical and primitive subtypes.

Molecular characterisation of TP53 mutated squamous cell carcinomas of the lung to identify putative targets for therapy