A new amplicon-based gene panel for next generation sequencing characterization of meningiomas
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A new amplicon-based gene panel for next generation sequencing characterization of meningiomas. / Mawrin, Christian; Koch, Ralf; Waldt, Natalie; Sandalcioglu, I Erol; Braunsdorf, Werner K; Warnke, Jan-Peter; Goehre, Felix; Meisel, Hans-Jürgen; Ewald, Christian; Neyazi, Sina; Schüller, Ulrich; Kirches, Elmar.
in: BRAIN PATHOL, Jahrgang 32, Nr. 2, e13046, 03.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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TY - JOUR
T1 - A new amplicon-based gene panel for next generation sequencing characterization of meningiomas
AU - Mawrin, Christian
AU - Koch, Ralf
AU - Waldt, Natalie
AU - Sandalcioglu, I Erol
AU - Braunsdorf, Werner K
AU - Warnke, Jan-Peter
AU - Goehre, Felix
AU - Meisel, Hans-Jürgen
AU - Ewald, Christian
AU - Neyazi, Sina
AU - Schüller, Ulrich
AU - Kirches, Elmar
PY - 2022/3
Y1 - 2022/3
N2 - 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%), AKT1E17K (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 KLF4K409Q/TRAF7 for secretory meningiomas and preferential skull base localization of meningiomas harboring SMO and AKT1E17K 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.
AB - 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%), AKT1E17K (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 KLF4K409Q/TRAF7 for secretory meningiomas and preferential skull base localization of meningiomas harboring SMO and AKT1E17K 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.
KW - Brain Neoplasms
KW - Chromosomal Proteins, Non-Histone
KW - DNA-Binding Proteins
KW - High-Throughput Nucleotide Sequencing
KW - Homozygote
KW - Humans
KW - Meningeal Neoplasms/genetics
KW - Meningioma/genetics
KW - Mutation
U2 - 10.1111/bpa.13046
DO - 10.1111/bpa.13046
M3 - SCORING: Review article
C2 - 35213080
VL - 32
JO - BRAIN PATHOL
JF - BRAIN PATHOL
SN - 1015-6305
IS - 2
M1 - e13046
ER -