Advertisement

Acta Neuropathologica

, Volume 109, Issue 6, pp 639–642 | Cite as

PIK3CA mutations in glioblastoma multiforme

  • Christian Hartmann
  • Gesine Bartels
  • Claire Gehlhaar
  • Nikola Holtkamp
  • Andreas von Deimling
Regular Paper

Abstract

Glioblastoma multiforme WHO grade IV is the most common and malignant variant of astrocytic tumors. Loss of heterozygosity of chromosome 10 and mutations in the tumor suppressor gene PTEN on 10q are molecular hallmarks of glioblastomas. Recently, mutations were identified in PIK3CA, encoding a protein that antagonizes the function of PTEN protein in the PI3K/Akt pathway. To address the question whether an exclusive mutation pattern can be observed in PIK3CA and PTEN, we determined the frequency of mutations in both genes. All coding exons were examined by single strand confirmation polymorphism and direct sequencing. Additionally, we analyzed chromosome 10 for loss of heterozygosity and evaluated the mutational status of TP53. In 70 glioblastomas, 5 (7%) PIK3CA mutations and 10 (14%) PTEN mutations were found. All mutations in PIK3CA located to exons 1, 9 and 20, thereby supporting the concept of mutational hot spot regions. In all but one glioblastoma, mutations were seen either in PIK3CA or in PTEN. In conclusion, the frequency of PIK3CA mutations in glioblastomas appears to be much lower than initially reported.

Keywords

Glioblastoma multiforme PIK3CA PTEN Chromosome 10 TP53 

References

  1. 1.
    Broderick DK, Di C, Parrett TJ, et al (2004) Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas. Cancer Res 64:5048–5050Google Scholar
  2. 2.
    Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296:1655–1657CrossRefPubMedGoogle Scholar
  3. 3.
    Duerr EM, Rollbrocker B, Hayashi Y, et al (1998) PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16:2259–2264CrossRefPubMedGoogle Scholar
  4. 4.
    Hartmann C, Numann A, Mueller W, et al (2004) Fine mapping of chromosome 22q tumor suppressor gene candidate regions in astrocytoma. Int J Cancer 108:839–844Google Scholar
  5. 5.
    Ichimura K, Bolin MB, Goike HM, et al (2000) Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1-S transition control gene abnormalities. Cancer Res 60:417–424PubMedGoogle Scholar
  6. 6.
    Kleihues P, Cavenee WK (2000) Pathology and genetics of tumours of the nervous system, 2nd edn. IARC Press, LyonGoogle Scholar
  7. 7.
    Knobbe CB, Reifenberger G (2003) Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-3’-kinase/protein kinase B (Akt) signal transduction pathway in glioblastomas. Brain Pathol 13:507–518PubMedGoogle Scholar
  8. 8.
    Louis DN, Deimling A von, Seizinger BR (1992) A (CA)n dinucleotide repeat assay for evaluating loss of allelic heterozygosity in small and archival human brain tumor specimens. Am J Pathol 141:777–782Google Scholar
  9. 9.
    Ma YY, Wei SJ, Lin YC, et al (2000) PIK3CA as an oncogene in cervical cancer. Oncogene 19:2739–2744Google Scholar
  10. 10.
    Miller CT, Moy JR, Lin L, et al (2003) Gene amplification in esophageal adenocarcinomas and Barrett’s with high-grade dysplasia. Clin Cancer Res 9:4819–4825Google Scholar
  11. 11.
    Racz A, Brass N, Heckel D, et al (1999) Expression analysis of genes at 3q26-q27 involved in frequent amplification in squamous cell lung carcinoma. Eur J Cancer 35:641–646Google Scholar
  12. 12.
    Rao RD, James CD (2004) Altered molecular pathways in gliomas: an overview of clinically relevant issues. Semin Oncol 31:595–604Google Scholar
  13. 13.
    Reifenberger G, Collins VP (2004) Pathology and molecular genetics of astrocytic gliomas. J Mol Med 82:656–670Google Scholar
  14. 14.
    Samuels Y, Wang Z, Bardelli A, et al (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304:554Google Scholar
  15. 15.
    Tong CY, Hui AB, Yin XL, et al (2004) Detection of oncogene amplifications in medulloblastomas by comparative genomic hybridization and array-based comparative genomic hybridization. J Neurosurg Spine 100:187–193Google Scholar
  16. 16.
    Woenckhaus J, Steger K, Werner E, et al (2002) Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma. J Pathol 198:335–342Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Christian Hartmann
    • 1
  • Gesine Bartels
    • 1
  • Claire Gehlhaar
    • 1
  • Nikola Holtkamp
    • 1
  • Andreas von Deimling
    • 1
  1. 1.Department of NeuropathologyCharité, Universitätsmedizin BerlinBerlinGermany

Personalised recommendations