Frequent mutation of the PIK3CA gene in ovarian and breast cancers.
OBJECTIVE
Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, resulting in increased cell proliferation, survival, and motility, is believed to play an oncogenic role in many cancer types. The PIK3CA gene encodes the p110alpha catalytic subunit of PI3K, and is amplified in some ovarian cancers, whereas the AKT2 gene is amplified in some ovarian, breast, and pancreatic cancers. Recently, in a mutational screen of eight PI3K genes and eight PI3K-like genes, PIK3CA was found to be the only gene affected by somatic mutations, which were observed frequently in gastrointestinal and brain cancers. Here, we test whether PIK3CA is subject to mutation in ovarian and breast cancers.


METHODS
Exons 9 and 20, encoding the highly conserved helical and kinase domains of PIK3CA, were subjected to sequence analysis in 198 advanced stage epithelial ovarian carcinomas and 72 invasive breast carcinomas (48 of ductal histology and 24 of lobular histology).


RESULTS
Somatic missense mutations were observed in 24 of 198 (12%) ovarian carcinomas, and in 13 of 72 (18%) breast carcinomas.


CONCLUSIONS
These data indicate that mutations of PIK3CA play an oncogenic role in substantial fractions of ovarian and breast carcinomas, and in consideration of mutation of other components of the PI3K-AKT pathway in both tumor types, confirm the major oncogenic role of this pathway in ovarian and breast carcinomas.
Levine
Douglas A
DA
Gynecology and Breast Research Laboratory, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Bogomolniy
Faina
F
Yee
Cindy J
CJ
Lash
Alex
A
Barakat
Richard R
RR
Borgen
Patrick I
PI
Boyd
Jeff
J
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D020134:Catalytic Domain / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics*; D017434:Protein Structure, Tertiary
D004273:DNA, Neoplasm; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human