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65th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

11 - 14 May 2014, Dresden

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Genome-wide CNV analysis identifies loci putatively associated with delayed time to first recurrence in IDH-mutant low-grade astrocytomas

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  • Tareq A Juratli - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus Dresden der Technischen Universität Dresden
  • Tim Lautenschlaeger - Department of Radiation Oncology, The Ohio State University Medical School, Columbus, Ohio, U.S.A.
  • Dietmar Krex - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus Dresden der Technischen Universität Dresden
  • Kathrin Geiger - Institut für Neuropathologie, Universitätsklinikum Carl Gustav Carus Dresden der Technischen Universität Dresden
  • Arnab Chakravarti - Department of Radiation Oncology, The Ohio State University Medical School, Columbus, Ohio, U.S.A.
  • Gabriele Schackert - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus Dresden der Technischen Universität Dresden

Deutsche Gesellschaft für Neurochirurgie. 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Dresden, 11.-14.05.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocP 048

doi: 10.3205/14dgnc444, urn:nbn:de:0183-14dgnc4447

Published: May 13, 2014

© 2014 Juratli et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: To identify copy number variations (CNVs) in IDH-mutated low-grade astrocytomas (LGA) predicting time to recurrence.

Method: LGA tissues and germline DNA from 17 LGA patients were analyzed. Tumor samples were assessed for IDH1/2 mutations and 1p/19q-codeletion. Analysis was performed using Affymetrix Genome-Wide Human SNP Array 6.0 and aroma.affymetrix package for R. After preprocessing with CRMAv2 segmentation by circular binary segmentation, only segments with 10 or more probes were included in CNV analysis. CNVs were called if the probe mean in each segment was greater than 1.5 for amplifications, and less than 0.75 for deletions, using germline DNA as reference. Union of segment borders resulted in 638 total segments. A proportional hazards model was fit with months to first recurrence as dependent variable for segments identified in two or more individuals. Genomic positions correspond to human genome build GRCh37 (UCSC hg19) and dbSNP build 131.

Results: Two cases had a 1p/19q-codeletion. Segmental deletions on 1p and 19q were associated with time to recurrence (1p35.1-p36.1 and 19q13.2-q13.43). For the following analysis excluding 1p/19q codeleted cases median time to first recurrence (n = 15) was 23 months. 21 autosomal segments were found in two or more patients. The maximum number of individuals with an aberration for any segment was three (chr5:57329584-57333534, chr6:103737977-103762062, chr8:144309756-144310618). Two segments were suggestively associated with time to first recurrence: chr5:197445-57839813 (raw-p = 0.085; risk ratio = 5.8) and chr8:144309756-144310618 (raw-p = 0.057; risk ratio = 5.3). Both amplifications and deletions were called on those chromosome 5 and chromosome 8 segments.

Conclusions: Suggestive associations of CNVs with time to first recurrence of IDH-mutated low-grade astrocytomas were identified. Segmental deletions on chromosomes 1 and 19 (when including 1p/19q codeleted cases) and aberrations on chromosomes 5 and 8 (in 1p/19q non-codeleted LGA) were suggestively associated with time to first recurrence.