PIK3CA gene mutations in pediatric and adult glioblastoma multiforme.

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

    Research output: Contribution to journalArticlepeer-review

    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 p110α 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.
    Original languageEnglish
    Pages (from-to)709-714
    Number of pages5
    JournalMolecular Cancer Research
    Volume4
    Issue number10
    DOIs
    Publication statusPublished - 31 Oct 2006

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