Lack of ROS1 Gene Rearrangement in Glioblastoma Multiforme.

Sun Min Lim,Jinyoung Sohn,Jong Hee Chang,Junjeong Choi,Frank Policht,Kristine Jacobson,John Schulz,Byoung Chul Cho,Se Hoon Kim,Eugene Andres Houseman

doi:10.1371/journal.pone.0137678

Sun Min Lim, Jinyoung Sohn + Show 8 more

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https://doi.org/10.1371/journal.pone.0137678

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Abstract

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, and the prognosis remains poor. Rearrangement of ROS1 gene, which was shown to have an oncogenic potential, was previously discovered in GBM cell lines. In this pilot study, we aimed to identify the incidence of ROS1 rearrangement in GBM patient tissues to explore novel biomarkers for therapeutic strategy. Formalin-fixed and paraffin-embedded (FFPE) tissue sections from 109 patients with GBM were screened for ROS1 rearrangement by anti-ROS immunohistochemistry (IHC) and ROS1 break-apart fluorescent in situ hybridization (FISH) assays. O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and Isocitrate dehydrogenase 1 (IDH1) mutation status were also assessed. All samples were interpreted by two experienced pathologists who were blinded to the clinical data. A total of 109 samples were collected and all samples were examined for ROS1 rearrangement by IHC and FISH assays, and none was found to harbor ROS1 rearrangement. MGMT gene methylation was found in 42 (39.2%) cases, and IDH1 mutation was found in 6 (5.5%) cases. In this study, ROS1 rearrangement was not identified in GBM patients, and thus it is difficult to classify ROS1 rearrangement as a novel molecular subset in GBM patients for now.

Highlights

Glioblastoma multiforme (GBM) is the most common type of primary brain tumors and the most aggressive subtype of high-grade gliomas
We aimed to identify the incidence of ROS1 rearrangement and evaluate clinicopathological features associated with ROS1 rearrangement in GBM patients
We performed IHC in 109 GBM patient samples and there was no positive staining for ROS1 (Fig 4A)

Summary

Introduction

Glioblastoma multiforme (GBM) is the most common type of primary brain tumors and the most aggressive subtype of high-grade gliomas. It is classified as grade IV in the World Health Organization classification of tumors of the central nervous system [1, 2]. The current standard treatment strategy for GBM patients consists of surgery followed by concurrent adjuvant radiotherapy in combination with temozolomide. Still less than 5% of patients survive longer than 5 years after diagnosis. The median overall survival is only 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone [3].

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