title: Phosphatidylinositol-3-kinase α catalytic subunit gene somatic mutations             in bronchopulmonary neuroendocrine tumours.
abstract: Bronchopulmonary neuroendocrine tumours (BP-NETs) comprise a large spectrum             of tumours including typical carcinoids (TCs), atypical carcinoids (ACs), large-cell             neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) that             exhibit considerably different biological aggressiveness and clinical behaviours.             The phosphatidylinositol-3-kinase α catalytic subunit (PIK3CA) gene is known to             be involved in the pathogenesis of several types of human cancers through gene             amplification, deletions or somatic missense mutations within the helical and             catalytic 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-NETs             by direct gene sequencing and to analyse its correlation with the main clinicopathological             parameters. To the best of our knowledge, we demonstrated for the first time a             high frequency of somatic missense mutations (23.2%) in the PIK3CA gene in a series             of 190 BP-NETs, including 75 TCs, 23 ACs, 17 LCNECs and 75 SCLCs. The frequency             of the PIK3CA gene mutation in the kinase domain was higher (17.9%) than that             in the helical domain (5.3%). When the mutational status of the PIK3CA gene was             compared with the main clinical and pathological characteristics of the BP-NET             patients, we found a significant association between PIK3CA gene mutations and             BP-NET histology (p=0.011). Interestingly, the frequency of PIK3CA gene mutations             increased with the biological aggressiveness of all BP-NETs, except LCNECs. In             conclusion, our results suggest that PIK3CA gene mutations may play a key role             in tumourigenesis and aggressiveness of BP-NETs. The PIK3CA gene may represent             a favourable candidate for an effective therapeutic strategy in the treatment             of patients with BP-NETs.
authors.affiliation: Department of Surgery, Division of Pathological Anatomy, University                     of Pisa, I-56124 Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Capodanno
authors.forename: Laura
authors.initials: L
authors.lastname: Boldrini
authors.forename: Greta
authors.initials: G
authors.lastname: Alì
authors.forename: Serena
authors.initials: S
authors.lastname: Pelliccioni
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mussi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000378:metabolism; D009490:Neurosecretory Systems / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt