Gamma Knife Radiosurgery does not alter the copy number aberration profile in sporadic vestibular schwannoma
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LABORATORY INVESTIGATION
Gamma Knife Radiosurgery does not alter the copy number aberration profile in sporadic vestibular schwannoma Aril Løge Håvik1,2,4 · Ove Bruland2 · Dhanushan Dhayalan3,4 · Morten Lund‑Johansen3,4 · Per‑Morten Knappskog1,2 Received: 28 May 2020 / Revised: 20 September 2020 / Accepted: 22 September 2020 © The Author(s) 2020
Abstract Introduction Ionizing radiation is a known etiologic factor in tumorigenesis and its role in inducing malignancy in the treatment of vestibular schwannoma has been debated. The purpose of this study was to identify a copy number aberration (CNA) profile or specific CNAs associated with radiation exposure which could either implicate an increased risk of malignancy or elucidate a mechanism of treatment resistance. Methods 55 sporadic VS, including 18 treated with Gamma Knife Radiosurgery (GKRS), were subjected to DNA wholegenome microarray and/or whole-exome sequencing. CNAs were called and statistical tests were performed to identify any association with radiation exposure. Hierarchical clustering was used to identify CNA profiles associated with radiation exposure. Results A median of 7 (0–58) CNAs were identified across the 55 VS. Chromosome 22 aberration was the only recurrent event. A median aberrant cell fraction of 0.59 (0.25–0.94) was observed, indicating several genetic clones in VS. No CNA or CNA profile was associated with GKRS. Conclusion GKRS is not associated with an increase in CNAs or alteration of the CNA profile in VS, lending support to its low risk. This also implies that there is no major issue with GKRS treatment failure being due to CNAs. In agreement with previous studies, chromosome 22 aberration is the only recurrent CNA. VS consist of several genetic clones, addressing the need for further studies on the composition of cells in this tumor. Keywords Vestibular schwannoma · Gamma Knife Radiosurgery · Whole genome microarray · Intratumor genetic heterogeneity · Neurosurgery · Genetics
Introduction
Morten Lund-Johansen and Per-Morten Knappskog have contributed equally to this work. * Morten Lund‑Johansen mljo@helse‑bergen.no * Per‑Morten Knappskog per.knappskog@helse‑bergen.no 1
Department of Clinical Science, University of Bergen, Bergen, Norway
2
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
3
Department of Clinical Medicine, University of Bergen, Bergen, Norway
4
Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway
Vestibular schwannoma (VS) is a benign intracranial neoplasm originating from the Schwann cells surrounding the vestibular portion of the 8th cranial nerve. VS makes up 8% of intracranial tumors, with an annual incidence rate ranging from 10 to 22 per million [1, 2]. Although patients have a normal life expectancy, they experience significantly reduced quality of life attributable to dizziness, headache, hearing loss, facial nerve palsy and tinnitus [3]. Inactivation of the NF2 tumor suppressor gene is considered an initiating eve
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