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PIK3CA alterations in primary (de novo) and secondary glioblastomas

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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%; P < 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.

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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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Authors and Affiliations

  1. International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon Cedex 08, France

    Daisuke Kita & Hiroko Ohgaki

  2. Department of Neurosurgery, University Hospital Zurich, 8091, Zurich, Switzerland

    Yasuhiro Yonekawa

  3. Department of Neurology, University of Tubingen Medical School, Tübingen, Germany

    Michael Weller

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  1. Daisuke Kita
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  4. Hiroko Ohgaki
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Correspondence to Hiroko Ohgaki.

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Kita, D., Yonekawa, Y., Weller, M. et al. PIK3CA alterations in primary (de novo) and secondary glioblastomas. Acta Neuropathol 113, 295–302 (2007). https://doi.org/10.1007/s00401-006-0186-1

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  • DOI: https://doi.org/10.1007/s00401-006-0186-1

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