Youngblood, Mark W., Duran, Daniel ORCID: 0000-0001-6888-252X, Montejo, Julio D., Li, Chang, Omay, Sacit Bulent, Ozduman, Koray, Sheth, Amar H., Zhao, Amy Y., Tyrtova, Evgeniya, Miyagishima, Danielle F., Fomchenko, Elena, I, Hong, Christopher S., Clark, Victoria E., Riche, Maximilien, Peyre, Matthieu, Boetto, Julien, Sohrabi, Sadaf, Koljaka, Sarah, Baranoski, Jacob F., Knight, James, Zhu, Hongda, Pamir, M. Necmettin, Avsar, Timucin, Kilic, Turker, Schramm, Johannes, Timmer, Marco, Goldbrunner, Roland, Gong, Ye, Bayri, Yasar, Amankulor, Nduka, Hamilton, Ronald L., Bilguvar, Kaya, Tikhonova, Irina, Tomak, Patrick R., Huttner, Anita, Simon, Matthias, Krischek, Boris, Kalamarides, Michel, Erson-Omay, E. Zeynep, Moliterno, Jennifer and Guenel, Murat (2020). Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas. J. Neurosurg., 133 (5). S. 1345 - 1355. ROLLING MEADOWS: AMER ASSOC NEUROLOGICAL SURGEONS. ISSN 1933-0693

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Abstract

OBJECTIVE Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts. METHODS Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features. RESULTS Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among mutation unknown samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation. CONCLUSIONS Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Youngblood, Mark W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duran, DanielUNSPECIFIEDorcid.org/0000-0001-6888-252XUNSPECIFIED
Montejo, Julio D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, ChangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Omay, Sacit BulentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ozduman, KorayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sheth, Amar H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhao, Amy Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tyrtova, EvgeniyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miyagishima, Danielle F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fomchenko, Elena, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hong, Christopher S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clark, Victoria E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riche, MaximilienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peyre, MatthieuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boetto, JulienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sohrabi, SadafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koljaka, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baranoski, Jacob F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knight, JamesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, HongdaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pamir, M. NecmettinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Avsar, TimucinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilic, TurkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schramm, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timmer, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldbrunner, RolandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gong, YeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bayri, YasarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amankulor, NdukaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamilton, Ronald L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bilguvar, KayaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tikhonova, IrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tomak, Patrick R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huttner, AnitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simon, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krischek, BorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kalamarides, MichelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erson-Omay, E. ZeynepUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moliterno, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenel, MuratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-313220
DOI: 10.3171/2019.8.JNS191266
Journal or Publication Title: J. Neurosurg.
Volume: 133
Number: 5
Page Range: S. 1345 - 1355
Date: 2020
Publisher: AMER ASSOC NEUROLOGICAL SURGEONS
Place of Publication: ROLLING MEADOWS
ISSN: 1933-0693
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MUTATIONS; AKT1; GRADE; SMO; EPENDYMOMAS; EXPRESSION; GERMLINE; TRAF7; KLF4Multiple languages
Clinical Neurology; SurgeryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31322

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