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Development of a rapid and comprehensive genomic profiling test supporting diagnosis and research for gliomas

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Abstract

A prompt and reliable molecular diagnosis for brain tumors has become crucial in precision medicine. While Comprehensive Genomic Profiling (CGP) has become feasible, there remains room for enhancement in brain tumor diagnosis due to the partial lack of essential genes and limitations in broad copy number analysis. In addition, the long turnaround time of commercially available CGPs poses an additional obstacle to the timely implementation of results in clinics. To address these challenges, we developed a CGP encompassing 113 genes, genome-wide copy number changes, and MGMT promoter methylation. Our CGP incorporates not only diagnostic genes but also supplementary genes valuable for research. Our CGP enables us to simultaneous identification of mutations, gene fusions, focal and broad copy number alterations, and MGMT promoter methylation status, with results delivered within a minimum of 4 days. Validation of our CGP, through comparisons with whole-genome sequencing, RNA sequencing, and pyrosequencing, has certified its accuracy and reliability. We applied our CGP for 23 consecutive cases of intracranial mass lesions, which demonstrated its efficacy in aiding diagnosis and prognostication. Our CGP offers a comprehensive and rapid molecular profiling for gliomas, which could potentially apply to clinical practices and research primarily in the field of brain tumors.

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Data availability

 Raw sequencing data of this study are available from the corresponding author on request.

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Acknowledgements

HS is supported by the Japan Society for the Promotion of Science KAKENHI (22H03190, 22K19591), National Cancer Center Research and Development Funds (2021-A-1), Japan Agency for Medical Research and Development (22ck0106693h0002, 23ck0106877h0001), MSD Life Science Foundation, Public Interest Incorporated Foundation, Japan Science and Technology Agency (21467119), Takeda Science Foundation, the Uehara Memorial Foundation, the Cell Science Research Foundation, and Astellas Foundation for Research on Metabolic Disorders. A.U. is supported by Kurozumi Medical Foundation. We thank National Cancer Center Research Institute Core Facility and Mai Honda-Kitahara for performing a part of panel-based sequencing. Blood samples of NCCH cases were provided by the National Cancer Center Biobank, Japan. Both the Core Facility and Biobank were supported in part by National Cancer Center Research and Development Fund, Japan. The super-computing resource was provided by Human Genome Center, The Institute of Medical Science, The University of Tokyo, and the NIG supercomputer at ROIS National Institute of Genetics.

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Authors and Affiliations

  1. Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Takuma Nakashima, Ryo Yamamoto, Yusuke Funakoshi, Shohei Nambu, Atsuhito Uneda & Hiromichi Suzuki

  2. Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan

    Takuma Nakashima, Ryo Yamamoto & Ryuta Saito

  3. Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Makoto Ohno, Masamichi Takahashi, Shunsuke Yanagisawa & Yoshitaka Narita

  4. Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Hirokazu Sugino

  5. Department of Neurosurgery, Dokkyo Medical University, 880 Kitakobaya-Shi, Mibu, Shimotsuga-Gun, Tochigi, 321-0293, Japan

    Takeo Uzuka

  6. Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-Cho Shogoin Sakyo-Ku, Kyoto, 606-8507, Japan

    Yoshiki Arakawa

  7. Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan

    Ryosuke Hanaya

  8. Department of Neurosurgery, Okayama University Graduate School of Medicine, 2-5-1 Shikata-Cho, Kita-Ku, Okayama, 700-8558, Japan

    Joji Ishida

  9. Department of Neurosurgery, Graduate School of Medical Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka City, 812-8582, Japan

    Koji Yoshimoto

Authors
  1. Takuma Nakashima
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  2. Ryo Yamamoto
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  3. Makoto Ohno
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  4. Hirokazu Sugino
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  5. Masamichi Takahashi
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  6. Yusuke Funakoshi
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  7. Shohei Nambu
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  8. Atsuhito Uneda
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  9. Shunsuke Yanagisawa
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  10. Takeo Uzuka
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  11. Yoshiki Arakawa
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  12. Ryosuke Hanaya
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  13. Joji Ishida
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  14. Koji Yoshimoto
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  15. Ryuta Saito
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  16. Yoshitaka Narita
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  17. Hiromichi Suzuki
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Contributions

HS led the study. TN and YF performed the bioinformatics analyses. TN, YF, SN, AU, RY, and HS designed a gene panel. MO, MT, TU, YA, RH, JI, KY, RS, and YN provided the patient material and expert advice. TN, RY, and HS prepared the manuscript, figures, and tables. All the authors read and approved the final manuscript.

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Correspondence to Hiromichi Suzuki.

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Nakashima, T., Yamamoto, R., Ohno, M. et al. Development of a rapid and comprehensive genomic profiling test supporting diagnosis and research for gliomas. Brain Tumor Pathol 41, 50–60 (2024). https://doi.org/10.1007/s10014-023-00476-3

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