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Acta Neuropathologica

, Volume 113, Issue 3, pp 295–302 | Cite as

PIK3CA alterations in primary (de novo) and secondary glioblastomas

  • Daisuke Kita
  • Yasuhiro Yonekawa
  • Michael Weller
  • Hiroko Ohgaki
Original Paper

Abstract

We assessed alterations in the EGFR/PTEN/PI3K pathway in 107 primary (de novo) glioblastomas and 32 secondary glioblastomas that progressed from low-grade or anaplastic astrocytomas. SSCP followed by DNA sequencing in exons 9 and 20 of the PIK3CA gene revealed missense mutations in 5/107 (5%) primary and 1/32 (3%) secondary glioblastomas. Quantitative real-time PCR showed PIK3CA amplification (>3 copy numbers) in 14/107 (13%) primary and 3/32 (9%) secondary glioblastomas. Only one glioblastoma showed both PIK3CA mutation and amplification. Taken together with previously published data on EGFR amplification and PTEN mutations, at least one alteration in the EGFR, PTEN, or PIK3CA genes was detected in 63% of primary glioblastomas, which was significantly more frequent than in secondary glioblastomas (31%; < 0.001). Furthermore, this signaling pathway was altered by either PTEN mutations or PIK3CA amplification in 10 of 12 (83%) malignant glioma cell lines analyzed. These results suggest that the EGFR/PTEN/PI3K pathway is frequently altered in glioblastomas and is a promising target for therapy, in particular for primary glioblastomas.

Keywords

PIK3CA mutation PIK3CA amplification PTEN mutations EGFR amplification Glioblastoma 

Notes

Acknowledgments

We thank Dr. Ole Laerum for kindly providing the DNA sample of OVCAR-3 cells with PIK3CA amplification. We thank Mrs Anne-Marie Camus for technical assistance. This work was supported by grants from the Foundation of Promotion of Cancer Research, Sumitomo Life Social Welfare Services Foundation, The Cell Science Research Foundation, and Hokkoku Cancer Foundation, Japan.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Daisuke Kita
    • 1
  • Yasuhiro Yonekawa
    • 2
  • Michael Weller
    • 3
  • Hiroko Ohgaki
    • 1
  1. 1.International Agency for Research on CancerLyon Cedex 08France
  2. 2.Department of NeurosurgeryUniversity Hospital ZurichZurichSwitzerland
  3. 3.Department of NeurologyUniversity of Tubingen Medical SchoolTübingenGermany

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