AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry

Felix Sahm, Juliane Bissel, Christian Koelsche, Leonille Schweizer, David Capper, David Reuss, Katja Böhmer, Ulrike Lass, Tanja Göck, Katrin Kalis, Jochen Meyer, Antje Habel, Stefanie Brehmer, Michel Mittelbronn, David T.W. Jones, Jens Schittenhelm, Steffi Urbschat, Ralf Ketter, Stephanie Heim, Christian MawrinJohannes A. Hainfellner, Anna Sophie Berghoff, Matthias Preusser, Albert Becker, Christel Herold-Mende, Andreas Unterberg, Christian Hartmann, Philipp Kickingereder, V. Peter Collins, Stefan M. Pfister, Andreas Von Deimling*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

85 Citations (Scopus)

Abstract

The activating E17K mutation in the AKT1 gene has been detected in several tumor entities. Currently several clinical studies with specific AKT1 inhibitors are under way. To determine whether AKT1 mutations are involved in human tumors of the nervous system, we examined a series of 1,437 tumors including 391 primary intracranial brain tumors and 1,046 tumors of the coverings of the central and peripheral nervous system. AKT1E17K mutations were exclusively seen in meningiomas and occurred in 65 of 958 of these tumors. A strong preponderance was seen in the variant of meningothelial meningioma WHO grade I of basal and spinal localization. In contrast, AKT1E17K mutations were rare in WHO grade II and absent in WHO grade III meningiomas. In order to more effectively detect this mutation, we tested for immunohistochemical markers associated with this alteration. We observed strong up-regulation of SFRP1 expression in all meningiomas with AKT1E17K mutation and in HEK293 cells after transfection with mutant AKT1E17K, but not in meningiomas and HEK293 cells lacking this mutation.

Original languageEnglish
Pages (from-to)757-762
Number of pages6
JournalActa Neuropathologica
Volume126
Issue number5
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

Keywords

  • AKT1
  • Immunohistochemistry
  • Meningioma
  • Meningothelial
  • SFRP1

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