Lan Jin1,2, Mark W Youngblood3, Trisha P Gupte1,2, Shaurey Vetsa1,2, Arushii Nadar1,2, Tanyeri Barak1,2, Kanat Yalcin1,2, Stephanie M Aguilera1,2, Ketu Mishra-Gorur1,2, Nicholas A Blondin2,4, Evan Gorelick1,2, S Bulent Omay1,2, Renelle Pointdujour-Lim2,5, Benjamin L Judson2,6, Michael Alperovich2,7, Mariam S Aboian2,8, Declan McGuone2,9, Murat Gunel1,2,10, Zeynep Erson-Omay1,2, Robert K Fulbright2,11, Jennifer Moliterno12,13. 1. Department of Neurosurgery, Yale School of Medicine, 15 York St, LLCI 810, New Haven, CT, 06520-8082, USA. 2. Yale Brain Tumor Center, Smilow Cancer Hospital, New Haven, CT, USA. 3. Department of Neurological Surgery, Northwestern University, Chicago, IL, USA. 4. Department of Clinical Neurology, Yale School of Medicine, New Haven, CT, USA. 5. Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT, USA. 6. Division of Otolaryngology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA. 7. Division of Plastic Surgery, Yale School of Medicine, New Haven, CT, USA. 8. Neuroradiology and Nuclear Medicine Sections, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA. 9. Department of Pathology, Yale School of Medicine, New Haven, CT, USA. 10. Department of Genetics, Yale School of Medicine, New Haven, CT, USA. 11. Neuroradiology Section, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA. 12. Department of Neurosurgery, Yale School of Medicine, 15 York St, LLCI 810, New Haven, CT, 06520-8082, USA. jennifermoliterno.gunel@yale.edu. 13. Yale Brain Tumor Center, Smilow Cancer Hospital, New Haven, CT, USA. jennifermoliterno.gunel@yale.edu.
Abstract
PURPOSE: As sphenoid wing meningiomas (SWMs) are associated with varying degrees of bony involvement, we sought to understand potential relationships between genomic subgroup and this feature. METHODS: Patients treated at Yale-New Haven Hospital for SWM were reviewed. Genomic subgroup was determined via whole exome sequencing, while the extent of bony involvement was radiographically classified as no bone invasion (Type I), hyperostosis only (Type II), tumor invasion only (Type III), or both hyperostosis and tumor invasion (Type IV). Among additional clinical variables collected, a subset of tumors was identified as spheno-orbital meningiomas (SOMs). Machine-learning approaches were used to predict genomic subgroups based on pre-operative clinical features. RESULTS: Among 64 SWMs, 53% had Type-II, 9% had Type-III, and 14% had Type-IV bone involvement; nine SOMs were identified. Tumors with invasion (i.e., Type III or IV) were more likely to be WHO grade II (p: 0.028). Additionally, tumors with invasion were nearly 30 times more likely to harbor NF2 mutations (OR 27.6; p: 0.004), while hyperostosis only were over 4 times more likely to have a TRAF7 mutation (OR 4.5; p: 0.023). SOMs were a significant predictor of underlying TRAF7 mutation (OR 10.21; p: 0.004). CONCLUSIONS: SWMs with invasion into bone tend to be higher grade and are more likely to be NF2 mutated, while SOMs and those with hyperostosis are associated with TRAF7 variants. Pre-operative prediction of molecular subtypes based on radiographic bony characteristics may have significant biological and clinical implications based on known recurrence patterns associated with genomic drivers and grade.
PURPOSE: As sphenoid wing meningiomas (SWMs) are associated with varying degrees of bony involvement, we sought to understand potential relationships between genomic subgroup and this feature. METHODS: Patients treated at Yale-New Haven Hospital for SWM were reviewed. Genomic subgroup was determined via whole exome sequencing, while the extent of bony involvement was radiographically classified as no bone invasion (Type I), hyperostosis only (Type II), tumor invasion only (Type III), or both hyperostosis and tumor invasion (Type IV). Among additional clinical variables collected, a subset of tumors was identified as spheno-orbital meningiomas (SOMs). Machine-learning approaches were used to predict genomic subgroups based on pre-operative clinical features. RESULTS: Among 64 SWMs, 53% had Type-II, 9% had Type-III, and 14% had Type-IV bone involvement; nine SOMs were identified. Tumors with invasion (i.e., Type III or IV) were more likely to be WHO grade II (p: 0.028). Additionally, tumors with invasion were nearly 30 times more likely to harbor NF2 mutations (OR 27.6; p: 0.004), while hyperostosis only were over 4 times more likely to have a TRAF7 mutation (OR 4.5; p: 0.023). SOMs were a significant predictor of underlying TRAF7 mutation (OR 10.21; p: 0.004). CONCLUSIONS: SWMs with invasion into bone tend to be higher grade and are more likely to be NF2 mutated, while SOMs and those with hyperostosis are associated with TRAF7 variants. Pre-operative prediction of molecular subtypes based on radiographic bony characteristics may have significant biological and clinical implications based on known recurrence patterns associated with genomic drivers and grade.
Authors: Stephanie M Robert; Shaurey Vetsa; Arushii Nadar; Sagar Vasandani; Mark W Youngblood; Evan Gorelick; Lan Jin; Neelan Marianayagam; E Zeynep Erson-Omay; Murat Günel; Jennifer Moliterno Journal: J Neurooncol Date: 2021-11-30 Impact factor: 4.130