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Revisiting the definition of glioma recurrence based on a phylogenetic investigation of primary and re-emerging tumor samples: a case report

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Abstract

A recurrent tumor is defined as a re-emerging subclone originating from an ancestorial clone of the primary neoplasm. Hence, it should be distinguished from de novo tumor emerging from other clones. Herein, we describe an exceptional case in which the locally re-emerging glioma did not share genetic alterations of the primary tumor. While the initial tumor harbored mutations in IDH1 and TERT genes as well as 1p/19q codeletion, the re-emerging tumor did not present any of these genetic abnormalities. Variant calling for tumor samples using whole-genome sequencing revealed that 1696 mutations within the primary tumor faded in the re-emerging tumor, and that 4591 mutations were newly detected in the re-emerging tumor. These results suggested that the initial and re-emerging tumors did not share same clonal origins, although the second tumor appeared adjacent to the old surgical cavity 5 years after the initial surgery. We finally speculated that the re-emerging tumor could be a “de novo glioma” or “radiation-induced glioblastoma following treatment of a diffuse glioma.” This case highlights the importance of molecular re-evaluation of clinically diagnosed “recurrent” glioma lesions.

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Availability of data and materials

The anonymized datasets analyzed in the present study are provided in supplementary information. The data of molecular profiling in this paper will be made freely available upon reasonable request.

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

Funding

This investigation was supported by JSPS KAKENHI 17K16646 (T.U.), 16K20006 (H.A.) and 20K09324 (H.A.), and AMED JP21gm0810011 (Y.K.) and JP21ck0106534 (Y.K.).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Toru Umehara, Hideyuki Arita, Takamune Achiha, Tomoyoshi Nakagawa, Manabu Kinoshita, Naoki Kagawa, Yasunori Fujimoto, Naoya Hashimoto & Haruhiko Kishima

  2. Department of Neurosurgery, Osaka International Cancer Institute, Osaka, Japan

    Hideyuki Arita

  3. Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Fuyuki Miya & Tatsuhiko Tsunoda

  4. Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan

    Fuyuki Miya & Tatsuhiko Tsunoda

  5. Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan

    Fuyuki Miya

  6. Department of Biomedical Research and Innovation, Institute for Clinical Research, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Tomoko Shofuda, Ema Yoshioka, Daisuke Kanematsu & Yonehiro Kanemura

  7. Department of Neurosurgery, Asahikawa Medical University, Asahikawa, Japan

    Manabu Kinoshita

  8. Department of Neurosurgery, Osaka Rosai Hospital, Sakai, Osaka, Japan

    Yasunori Fujimoto

  9. Department of Neurosurgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Naoya Hashimoto

  10. Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan

    Hiroki Kiyokawa & Eiichi Morii

  11. Laboratory for Medical Science Mathematics, Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan

    Tatsuhiko Tsunoda

  12. Laboratory for Medical Science Mathematics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan

    Tatsuhiko Tsunoda

  13. Department of Neurosurgery, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Yonehiro Kanemura

Authors
  1. Toru Umehara
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  2. Hideyuki Arita
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  3. Fuyuki Miya
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  4. Takamune Achiha
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  8. Tomoyoshi Nakagawa
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  16. Yonehiro Kanemura
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  17. Haruhiko Kishima
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Contributions

TU, HA, YK and HKis had major roles in the study concept and design. YF, NH and EM contributed to the clinical management of the patient and sample acquisitions. TU, TA, TS, EY, DK, and TN conducted the molecular studies. HKiy and EM conducted the pathological examination. TU, HA, FM, TS and YK contributed to analysis of data. TU, HA, FM, MK, NK, TT and YK contributed to interpretation of data. TU, HA and FM were major contributors in writing the manuscript. MK, NK, EM, TT and HKis revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hideyuki Arita.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Genetic analysis was conducted following approval by the internal ethical review boards of Osaka University Graduate School of Medicine (approval number: 13244). Written informed consent to participation and publication was obtained from the patient.

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Umehara, T., Arita, H., Miya, F. et al. Revisiting the definition of glioma recurrence based on a phylogenetic investigation of primary and re-emerging tumor samples: a case report. Brain Tumor Pathol 39, 218–224 (2022). https://doi.org/10.1007/s10014-022-00438-1

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  • DOI: https://doi.org/10.1007/s10014-022-00438-1

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