PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas.
OBJECTIVE
Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene in various human solid tumors. More than 75% of those somatic mutations are clustered in the helical (exon 9) and kinase domains (exon 20). The three hot-spot mutations, E542K, E545K, and H1047R, have been proven to elevate the lipid kinase activity of PIK3CA and activate the Akt signaling pathway. The mutational status of PIK3CA in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) has not been evaluated previously.


METHODS
To evaluate a possible role for PIK3CA in the tumorigenesis of IPMN and IPMC, exons 1, 4, 5, 6, 7, 9, 12, 18, and 20 were analyzed in 36 IPMN/IPMC and two mucinous cystadenoma specimens by direct genomic DNA sequencing.


RESULTS
We identified four missense mutations in the nine screened exons of PIK3CA from 36 IPMN/IPMC specimens (11%). One of the four mutations, H1047R, has been previously reported as a hot-spot mutation. The remaining three mutations, T324I, W551G, and S1015F, were novel and somatic.


CONCLUSIONS
This is the first report of PIK3CA mutation in pancreatic cancer. Our data provide evidence that the oncogenic properties of PIK3CA contribute to the tumorigenesis of IPMN/IPMC.
Schönleben
Frank
F
Department of Otolaryngology/Head and Neck Surgery, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA. gs2157@columbia.edu
Qiu
Wanglong
W
Ciau
Nancy T
NT
Ho
Daniel J
DJ
Li
Xiaojun
X
Allendorf
John D
JD
Remotti
Helen E
HE
Su
Gloria H
GH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human