ABSTRACT
Lung cancer still remains the leading cause of cancer-related mortality worldwide. Among the emerging biomarkers predictive for target therapy, Erythroblastic oncogene B (ERBB2) is recommended by the main international guidelines to be investigate, according to several novel therapeutic approaches. Aim of this retrospective study was to analyze the distribution of ERBB2 mutations and their location along the gene in a set of 331 consecutive lung cancer tissues analyzed by next generation sequencing (NGS) technology in the Structure of Oncological Molecular Pathology, Azienda USL Toscana Centro, Italy. ERBB2 variants were detected in 95 out 331 samples (28.7%) and statistical analysis showed a 3% distribution of oncogenic variants, in line with literature data. Moreover, NGS technology allowed to identify a substantial amount of transmembrane domain mutations, not detectable by single hot spot assay: they should represent future clinical target in lung cancer, since nowadays many trials are investigating their clinical benefit.

IMPACT STATEMENT
This report examined the distribution of entire ERBB2 variants along the protein structure and the frequency of oncogenic ones in a set of lung cancer samples.