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Gene expression profiling of 19q-loss astrocytomas suggest a specific pattern associated with the better prognosis

  • Clinical Study
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Abstract

Purpose

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. The aim of this study was to further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior.

Methods

We compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis.

Results

By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas, 102 up-regulated genes and 162 down-regulated genes were extracted. The down-regulated genes clustered heavily to 19q and 4p while the up-regulated genes clustered to 4q. It was noteworthy that fibroblast growth factor 1 associated with stem cell maintenance and multiple genes associated with glioma progression were down-regulated in 19q-loss astrocytomas, and these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, the expression pattern of the 19q-loss astrocytomas showed no shift toward oligodendrogliomas with 1p/19q codeletion but rather constituted a subgroup of astrocytoma.

Conclusions

These findings suggested that 19q-loss in astrocytomas is more likely acquired event rather than an early event in oncogenesis like the 1p/19q-codeletion in oligodendrogliomas, and that the biological features of 19q-loss astrocytomas are possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

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Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Acknowledgements

We are grateful to the patients for the donation of their tissue for research and acknowledge the excellent technical assistance of Ms. Kayoko Iwata of the Dokkyo Medical University laboratory.

Funding

This work was supported by a MEXT KAKENHI Grant to R.O (No. JP18K15286).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan

    Ryohei Otani

  2. Department of Neurosurgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan

    Ryohei Otani, Takeo Uzuka, Fumi Higuchi, Hadzki Matsuda, Phyo Kim & Keisuke Ueki

  3. Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

    Akitake Mukasa

  4. Department of Neurosurgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Masashi Nomura & Shota Tanaka

Authors
  1. Ryohei Otani
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  2. Akitake Mukasa
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  3. Takeo Uzuka
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  4. Fumi Higuchi
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  7. Shota Tanaka
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  8. Phyo Kim
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  9. Keisuke Ueki
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Contributions

All authors contributed to the study conception and design. Material preparation was performed by RO, TU, FH, and KU. Data analysis was performed by RO, AM, and KU. The first draft of the manuscript was written by RO and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ryohei Otani.

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Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethical approval

All experiments using human samples were approved by the ethics committee at Dokkyo Medical University (No.1431 and 24053).

Consent to participate

Written informed consent was obtained from all individual participants included in the study.

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Patients signed informed consent regarding publishing their data.

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Otani, R., Mukasa, A., Uzuka, T. et al. Gene expression profiling of 19q-loss astrocytomas suggest a specific pattern associated with the better prognosis. J Neurooncol 154, 221–228 (2021). https://doi.org/10.1007/s11060-021-03816-5

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  • DOI: https://doi.org/10.1007/s11060-021-03816-5

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