Phosphatidylinositol-3-kinase α catalytic subunit gene somatic mutations in bronchopulmonary neuroendocrine tumours

Bronchopulmonary neuroendocrine tumours (BP-NETs) comprise a large spectrumof tumours including typical carcinoids (TCs), atypical carcinoids (ACs), large-cellneuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) thatexhibit considerably different biological aggressiveness and clinical behaviours.The phosphatidylinositol-3-kinase α catalytic subunit (PIK3CA) gene is known tobe involved in the pathogenesis of several types of human cancers through geneamplification, deletions or somatic missense mutations within the helical andcatalytic domains. However, the PIK3CA gene status in BP-NETs has yet to be explored.This study aimed to investigate the PIK3CA gene status in a large series of BP-NETsby direct gene sequencing and to analyse its correlation with the main clinicopathologicalparameters. To the best of our knowledge, we demonstrated for the first time ahigh frequency of somatic missense mutations (23.2%) in the PIK3CA gene in a seriesof 190 BP-NETs, including 75 TCs, 23 ACs, 17 LCNECs and 75 SCLCs. The frequencyof the PIK3CA gene mutation in the kinase domain was higher (17.9%) than thatin the helical domain (5.3%). When the mutational status of the PIK3CA gene wascompared with the main clinical and pathological characteristics of the BP-NETpatients, we found a significant association between PIK3CA gene mutations andBP-NET histology (p=0.011). Interestingly, the frequency of PIK3CA gene mutationsincreased with the biological aggressiveness of all BP-NETs, except LCNECs. Inconclusion, our results suggest that PIK3CA gene mutations may play a key rolein tumourigenesis and aggressiveness of BP-NETs. The PIK3CA gene may representa favourable candidate for an effective therapeutic strategy in the treatmentof patients with BP-NETs.