Lack of ROS1 Gene Rearrangement in Glioblastoma Multiforme

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

doi:10.1371/journal.pone.0137678

Lack of ROS1 Gene Rearrangement in Glioblastoma Multiforme

PLoS One. 2015 Sep 14;10(9):e0137678. doi: 10.1371/journal.pone.0137678. eCollection 2015.

Authors

Sun Min Lim¹, Junjeong Choi², Jong Hee Chang³, Jinyoung Sohn⁴, Kristine Jacobson⁵, Frank Policht⁵, John Schulz⁵, Byoung Chul Cho¹, Se Hoon Kim⁶

Affiliations

¹ Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea.
² Department of Pharmacy, College of Pharmacy, Yonsei University, Seoul, Korea.
³ Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea.
⁴ JE-UK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Korea.
⁵ Abbott Molecular Diagnostics, Des Plaines, Illinois, United States of America.
⁶ Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers / metabolism
DNA Methylation
DNA Modification Methylases / genetics
DNA Repair Enzymes / genetics
Female
Gene Rearrangement*
Glioblastoma / diagnosis
Glioblastoma / genetics*
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Isocitrate Dehydrogenase / genetics
Male
Middle Aged
Multivariate Analysis
Pilot Projects
Prognosis
Promoter Regions, Genetic
Protein-Tyrosine Kinases / genetics*
Proto-Oncogene Proteins / genetics*
Tumor Suppressor Proteins / genetics

Substances

Biomarkers
Proto-Oncogene Proteins
Tumor Suppressor Proteins
Isocitrate Dehydrogenase
IDH1 protein, human
DNA Modification Methylases
MGMT protein, human
Protein-Tyrosine Kinases
ROS1 protein, human
DNA Repair Enzymes

Grants and funding

This work was funded by the Novartis Pharmaceuticals and a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C1186 to BCC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Jinyoung Sohn is employed by JEUK Co., Ltd. John Schulz is employed by Abbott Molecular Diagnostics. JEUK Co., Ltd and Abbott Molecular Diagnostics provided support in the form of salaries for authors Jinyoung Sohn and John Schulz respectively, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.