PMID- 22949056
OWN - NLM
STAT- MEDLINE
DCOM- 20130314
LR  - 20240513
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 28
IP  - 5
DP  - 2012 Nov
TI  - Phosphatidylinositol-3-kinase alpha catalytic subunit gene somatic mutations in 
      bronchopulmonary neuroendocrine tumours.
PG  - 1559-66
LID - 10.3892/or.2012.2017 [doi]
AB  - 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 alpha 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.
FAU - Capodanno, Alessandra
AU  - Capodanno A
AD  - Department of Surgery, Division of Pathological Anatomy, University of Pisa, 
      I-56124 Pisa, Italy.
FAU - Boldrini, Laura
AU  - Boldrini L
FAU - Ali, Greta
AU  - Ali G
FAU - Pelliccioni, Serena
AU  - Pelliccioni S
FAU - Mussi, Alfredo
AU  - Mussi A
FAU - Fontanini, Gabriella
AU  - Fontanini G
LA  - eng
PT  - Journal Article
DEP - 20120904
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (PIK3CA protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Class I Phosphatidylinositol 3-Kinases
MH  - Female
MH  - Gene Amplification
MH  - Humans
MH  - Lung Neoplasms/*genetics/metabolism
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Mutation, Missense
MH  - Neuroendocrine Tumors/*genetics/metabolism
MH  - Neurosecretory Systems/pathology
MH  - Phosphatidylinositol 3-Kinases/*genetics
MH  - Proto-Oncogene Proteins c-akt/genetics
MH  - Signal Transduction
MH  - Young Adult
PMC - PMC3583575
EDAT- 2012/09/06 06:00
MHDA- 2013/03/15 06:00
PMCR- 2012/09/04
CRDT- 2012/09/06 06:00
PHST- 2012/06/19 00:00 [received]
PHST- 2012/08/03 00:00 [accepted]
PHST- 2012/09/06 06:00 [entrez]
PHST- 2012/09/06 06:00 [pubmed]
PHST- 2013/03/15 06:00 [medline]
PHST- 2012/09/04 00:00 [pmc-release]
AID - or-28-05-1559 [pii]
AID - 10.3892/or.2012.2017 [doi]
PST - ppublish
SO  - Oncol Rep. 2012 Nov;28(5):1559-66. doi: 10.3892/or.2012.2017. Epub 2012 Sep 4.