DNA methylation subclass receptor tyrosine kinase II (RTK II) is predictive for seizure development in glioblastoma patients

Author:

Ricklefs Franz L1ORCID,Drexler Richard1,Wollmann Kathrin1,Eckhardt Alicia234,Heiland Dieter H5,Sauvigny Thomas1,Maire Cecile1,Lamszus Katrin1,Westphal Manfred1ORCID,Schüller Ulrich23ORCID,Dührsen Lasse1

Affiliation:

1. Department of Neurosurgery, University Medical Center Hamburg-Eppendorf , Hamburg , Germany

2. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany

3. Research Institute Children’s Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf , Hamburg , Germany

4. Department of Radiation Hematology and Oncology, University Medical Center Hamburg-Eppendorf , Hamburg , Germany

5. Department of Neurosurgery, Medical Center University of Freiburg , Freiburg , Germany (D.H.H.)

Abstract

Abstract Background Seizures can present at any time before or after the diagnosis of a glioma. Roughly, 25%–30% of glioblastoma (GBM) patients initially present with seizures, and an additional 30% develop seizures during the course of the disease. Early studies failed to show an effect of general administration of antiepileptic drugs for glioblastoma patients, since they were unable to stratify patients into high- or low-risk seizure groups. Methods 111 patients, who underwent surgery for a GBM, were included. Genome-wide DNA methylation profiling was performed, before methylation subclasses and copy number changes inferred from methylation data were correlated with clinical characteristics. Independently, global gene expression was analyzed in GBM methylation subclasses from TCGA datasets (n = 68). Results Receptor tyrosine Kinase (RTK) II GBM showed a significantly higher incidence of seizures than RTK I and mesenchymal (MES) GBM (P < .01). Accordingly, RNA expression datasets revealed an upregulation of genes involved in neurotransmitter synapses and vesicle transport in RTK II glioblastomas. In a multivariate analysis, temporal location (P = .02, OR 5.69) and RTK II (P = .03, OR 5.01) were most predictive for preoperative seizures. During postoperative follow-up, only RTK II remained significantly associated with the development of seizures (P < .01, OR 8.23). Consequently, the need for antiepileptic medication and its increase due to treatment failure was highly associated with the RTK II methylation subclass (P < .01). Conclusion Our study shows a strong correlation of RTK II glioblastomas with preoperative and long-term seizures. These results underline the benefit of molecular glioblastoma profiling with important implications for postoperative seizure control.

Funder

Fördergemeinschaft Kinderkrebszentrum Hamburg

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Neurology (clinical),Oncology

Cited by 10 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3