AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry
The activating E17K mutation in the AKT1 gene has been detected in several tumor entities. Currently several clinical studies with specific AKTI 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 incl...
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Published in | Acta neuropathologica Vol. 126; no. 5; p. 757 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Springer
01.11.2013
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Abstract | The activating E17K mutation in the AKT1 gene has been detected in several tumor entities. Currently several clinical studies with specific AKTI 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 upregulation of SFRPI 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. Keywords Meningioma * Meningothelial * AKT1 * Immunohistochemistry * SFRP1 |
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AbstractList | The activating E17K mutation in the AKT1 gene has been detected in several tumor entities. Currently several clinical studies with specific AKTI 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 upregulation of SFRPI 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. The activating E17K mutation in the AKT1 gene has been detected in several tumor entities. Currently several clinical studies with specific AKTI 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 upregulation of SFRPI 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. Keywords Meningioma * Meningothelial * AKT1 * Immunohistochemistry * SFRP1 |
Audience | Academic |
Author | Gock, Tanja Meyer, Jochen Hainfellner, Johannes A Schweizer, Leonille Sahm, Felix Reuss, David Brehmer, Stefanie Ketter, Ralf Habel, Antje Koelsche, Christian Pfister, Stefan M Heim, Stephanie Mittelbronn, Michel Preusser, Matthias Becker, Albert Kalis, Katrin Schittenhelm, Jens Kickingereder, Philipp Bissel, Juliane Unterberg, Andreas Berghoff, Anna-Sophie Herold-Mende, Christel Collins, V. Peter Hartmann, Christian Jones, David T.W von Deimling, Andreas Urbschat, Steffi Capper, David Mawrin, Christian Bohmer, Katja Lass, Ulrike |
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Title | AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry |
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