A new amplicon-based gene panel for next generation sequencing characterization of meningiomas.

Autor: Mawrin C; Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany., Koch R; Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany., Waldt N; Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany., Sandalcioglu IE; Department of Neurosurgery, Otto-von-Guericke-University, Magdeburg, Germany., Braunsdorf WEK; Department of Neurosurgery, City Hospital Magdeburg, Magdeburg, Germany., Warnke JP; Department of Neurosurgery, Paracelsus-Hospital Zwickau, Zwickau, Germany., Goehre F; Department of Neurosurgery, Bergmannstrost Hospital Halle/Saale, Halle/Saale, Germany., Meisel HJ; Department of Neurosurgery, Bergmannstrost Hospital Halle/Saale, Halle/Saale, Germany., Ewald C; Department of Neurosurgery, Brandenburg Medical School, Brandenburg an der Havel, Germany., Neyazi S; Department of Pediatric Hematology and Oncology, University Hospital Hamburg, Hamburg, Germany.; Research Institute Children's Cancer Center, Hamburg, Germany., Schüller U; Department of Pediatric Hematology and Oncology, University Hospital Hamburg, Hamburg, Germany.; Research Institute Children's Cancer Center, Hamburg, Germany.; Department of Neuropathology, University Hospital Hamburg, Hamburg, Germany., Kirches E; Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany.
Jazyk: angličtina
Zdroj: Brain pathology (Zurich, Switzerland) [Brain Pathol] 2022 Mar; Vol. 32 (2), pp. e13046.
DOI: 10.1111/bpa.13046
Abstrakt: Meningiomas are the most frequent primary intracranial tumors. The considerable variety of histological subtypes has been expanded by the definition of molecular alterations, which can improve both diagnostic accuracy and determination of individual patient's outcome. According to the upcoming WHO classification of brain tumors, the in-time analysis of frequent molecular events in meningiomas may become mandatory to define meningioma subtypes. We have compiled a custom-made amplicon-based next generation sequencing (NGS) meningioma panel covering the most frequent known recurrent mutations in 15 different genes. In an unselected consecutive meningioma cohort (109 patients) analyzed over a period of 12 months, we detected mutations in 11 different genes, with most frequent alterations in NF2 (43%), AKT1 E17K (15%), and TRAF7 (13%). In 39 tumors (36%), two different mutations were detected, with NF2 and SUFU (n = 5) and KLF4 and TRAF7 (n = 5) being the most frequent combinations. No alterations were found in POLR2A, CDKN2A, CDKN2B, and BAP1, and no homozygous CDKN2A/B deletion was detected. NF2 mutations were found in tumors of all WHO grades, whereas mutations in KLF4, TRAF7, and SMO were restricted to WHO grade I meningiomas. In contrast, SMARCE1 and TERT mutations were associated with WHO grade II meningiomas (according to the WHO classification 2016). The distribution of mutations across histological subtypes or tumor localization was in line with the existing literature, with typical combinations like KLF4K 409Q /TRAF7 for secretory meningiomas and preferential skull base localization of meningiomas harboring SMO and AKT1 E17K mutations. Thus, we present a custom-made NGS meningioma panel providing a time and cost-efficient reliable detection of relevant somatic molecular alterations in meningiomas suitable for daily routine.
(© 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)
Databáze: MEDLINE
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