Lung squamous cell carcinomas with basaloid histology represent a specific molecular entity.

Purpose: The basaloid carcinoma (pure) and the (mixed) basaloid variant of lung squamous cell carcinoma (SCC) have a dismal prognosis but their underlying specific molecular characteristics remain obscure and no therapy has proven to be efficient.

Experimental Design: To assess their molecular specificity among other lung SCCs we analyzed DNA copy number aberrations and mRNA expression pangenomic profiles of 93 SCCs, including 42 basaloid samples (24 pure, 18 mixed).

Results: Supervised analyses reveal that pure basaloid tumors display a specific mRNA expression profile, encoding factors controlling the cell cycle, transcription, chromatin, and splicing, with prevalent expression in germline and stem cells, while genes related to squamous differentiation are underexpressed.