Document Detail


PIK3CA gene mutations in pediatric and adult glioblastoma multiforme.
MedLine Citation:
PMID:  17050665     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Gary L Gallia; Vikki Rand; I-Mei Siu; Charles G Eberhart; C David James; Suely K N Marie; Sueli M Oba-Shinjo; Carlos G Carlotti; Otavia L Caballero; Andrew J G Simpson; Malcolm V Brock; Pierre P Massion; Benjamin S Carson; Gregory J Riggins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  4     ISSN:  1541-7786     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-19     Completed Date:  2007-02-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  709-14     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II, Room 257, Baltimore, MD 21231, USA.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / genetics*
Adolescent
Aged
Child
Gene Amplification
Genetic Predisposition to Disease*
Genetic Testing
Glioblastoma / genetics*
Humans
Middle Aged
Mutation*
Polymorphism, Single-Stranded Conformational
Transplantation, Heterologous
Chemical
Reg. No./Substance:
EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.1.137/PIK3CA protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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