title: PIK3CA gene mutations in pediatric and adult glioblastoma multiforme.
abstract: The phosphatidylinositol 3-kinases (PI3K) are a family of enzymes that relay important cellular growth control signals. Recently, a large-scale mutational analysis of eight PI3K and eight PI3K-like genes revealed somatic mutations in PIK3CA, which encodes the p110alpha catalytic subunit of class IA PI3K, in several types of cancer, including glioblastoma multiforme. In that report, 4 of 15 (27%) glioblastomas contained potentially oncogenic PIK3CA mutations. Subsequent studies, however, showed a significantly lower mutation rate ranging from 0% to 7%. Given this disparity and to address the relation of patient age to mutation frequency, we examined 10 exons of PIK3CA in 73 glioblastoma samples by PCR amplification followed by direct DNA sequencing. Overall, PIK3CA mutations were found in 11 (15%) samples, including several novel mutations. PIK3CA mutations were distributed in all sample types, with 18%, 9%, and 13% of primary tumors, xenografts, and cell lines containing mutations, respectively. Of the primary tumors, PIK3CA mutations were identified in 21% and 17% of pediatric and adult samples, respectively. No evidence of PIK3CA gene amplification was detected by quantitative real-time PCR in any of the samples. This study confirms that PIK3CA mutations occur in a significant number of human glioblastomas, further indicating that therapeutic targeting of this pathway in glioblastomas is of value. Moreover, this is the first study showing PIK3CA mutations in pediatric glioblastomas, thus providing a molecular target in this important pediatric malignancy.
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II, Room 257, Baltimore, MD 21231, USA.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Gallia
authors.forename: Vikki
authors.initials: V
authors.lastname: Rand
authors.forename: I-Mei
authors.initials: IM
authors.lastname: Siu
authors.forename: Charles G
authors.initials: CG
authors.lastname: Eberhart
authors.forename: C David
authors.initials: CD
authors.lastname: James
authors.forename: Suely K N
authors.initials: SK
authors.lastname: Marie
authors.forename: Sueli M
authors.initials: SM
authors.lastname: Oba-Shinjo
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Carlotti
authors.forename: Otavia L
authors.initials: OL
authors.lastname: Caballero
authors.forename: Andrew J G
authors.initials: AJ
authors.lastname: Simpson
authors.forename: Malcolm V
authors.initials: MV
authors.lastname: Brock
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Massion
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Carson
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
mesh_terms: D000293:Adolescent; D000368:Aged; D002648:Child; D058534:Class I Phosphatidylinositol 3-Kinases; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D014183:Transplantation, Heterologous
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human