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Comparison of 1p and 19q status of glioblastoma by whole exome sequencing, array-comparative genomic hybridization, and fluorescence in situ hybridization

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Abstract

According to the 2016 World Health Organization classification of tumors of the central nervous system, detecting 1p/19q co-deletion became essential in clinical neuropathology for gliomas with oligodendroglioma-like morphology. Here, we assessed genomic profiles of glioblastoma in 80 cases including 1p/19q status using fluorescent in situ hybridization (FISH), array-comparative genomic hybridization (aCGH), and/or whole exome sequencing (WES). Paraffin-embedded tumor tissues were subjected to FISH analysis, and the corresponding frozen tissues from the same tumors were evaluated for aCGH and/or WES for 1p/19q co-deletion and other genetic parameters, which included IDH1-R132H, ATRX, TP53, CIC, and NOTCH1 mutations and MGMT methylation status. We also evaluated correlations between 1p/19q co-deletion status and molecular markers or clinical outcomes. The FISH analyses revealed 1p/19q co-deletion in two cases, isolated deletion of 1p in six cases, and 19q in two cases, whereas the aCGH and WES results showed isolated deletion of 19q in four cases and 19 monosomy in only one case. Eleven cases showed discordant 1p/19q results between aCGH/WES and FISH analysis, and in most of them, 1p and/or 19q deletion on FISH analysis corresponded to the partial deletions at 1p36 and/or 19q13 on aCGH/WES. Our cohort exhibited IDH1-R132H mutations (5.4%), MGMT promotor methylation (34.6%), and mutations in ATRX (9.5%), TP53 (33.3%), and NOTCH1 (3.8%) but not in CIC (0%). In addition, MGMT methylation and ATRX mutation were significantly associated with clinical prognosis. In glioblastomas, partial deletions of 1p36 and/or 19q13 were uncommon, some of which appeared as 1p and/or 19q deletions on FISH analysis.

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Acknowledgements

This work was supported by a grant of the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (HI14C3418).

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  1. Jongmin Sim and Do-Hyun Nam contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea

    Jongmin Sim, Yuil Kim & Yeon-Lim Suh

  2. Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

    Do-Hyun Nam & Jung Won Choi

  3. Samsung Biomedical Research Institute, and Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Republic of Korea

    In-Hee Lee & Jason K. Sa

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  1. Jongmin Sim
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Sim, J., Nam, DH., Kim, Y. et al. Comparison of 1p and 19q status of glioblastoma by whole exome sequencing, array-comparative genomic hybridization, and fluorescence in situ hybridization. Med Oncol 35, 60 (2018). https://doi.org/10.1007/s12032-018-1119-2

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