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

作者：Sahm Felix; Bissel Juliane; Koelsche Christian; Schweizer Leonille; Capper David; Reuss David; Boehmer Katja; Lass Ulrike; Goeck Tanja; Kalis Katrin; Meyer Jochen; Habel Antje; Brehmer Stefanie; Mittelbronn Michel; Jones David T W; Schittenhelm Jens; Urbschat Steffi; Ketter Ralf; Heim Stephanie; Mawrin Christian; Hainfellner Johannes A; Berghoff Anna Sophie; Preusser Matthias; Becker Albert; Herold Mende Christel; Unterberg Andreas; Hartmann Christian

来源：Acta Neuropathologica, 2013, 126(5): 757-762.

DOI：10.1007/s00401-013-1187-5

• Meningioma
• Meningothelial
• AKT1
• Immunohistochemistry
• SFRP1

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.

• 出版日期2013-11