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Incidence, clinicopathologic, and genetic characteristics of mismatch repair gene-mutated glioblastomas

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Background

Glioblastoma (GBM) is the most common and malignant gliomas of adults and recur, resulting in death, despite surgery, radiotherapy, and temozolomide-based chemotherapy. There are a few reports on immunotherapy for the mismatch repair (MMR)-deficient GBMs with high tumor mutational burden (TMB). However, the clinicopathological and genetic features of the MMR genes altered in GBMs have not been elucidated yet.

Methods

The authors analyzed targeted next-generation sequencing (NGS) data from 282 (276 primary and 6 recurrent) glioblastomas to evaluate the mutational status of six DNA repair-related genes: MLH1, MSH2, MSH6, PMS2, POLE, and POLD1. Tumors harboring somatic or germline mutations in one or more of these six genes were classified as an MMR gene-altered GBM. The clinicopathologic and molecular characteristics of MMR gene-altered GBMs were compared to those of tumors without MMR gene alterations.

Results

Sixty germline or somatic mutations were identified in 37 cases (35 primary and two recurrent) of GBM. The most frequently mutated genes were MSH6 and POLE. Single nucleotide variants were the most common, followed by frameshift deletions or insertions and approximately 60% of the mutations were germline mutations. Two patients who showed MSH2 (c.2038C > T) and MSH6 (c.1082G > A) mutations had familial colon cancer. The clinical findings were not different between the two groups. However, the presence of MGMT promoter methylation and high tumor mutation burden (TMB) values (> 20) were correlated with MMR gene alterations.

Conclusion

Since MMR-related genes can be found even in primary glioblastoma and are correlated with high TMB and MGMT promoter methylation, MMR genes should be carefully analyzed in NGS study on glioblastomas.

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Data availability

The data generated and analyzed in this study are provided in the text and the figures, tables, and supplementary tables. Any additional data needed may be requested from the corresponding author.

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Authors and Affiliations

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

    Yoon Ah Cho & Yeon-Lim Suh

  2. Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea

    Yoon Ah Cho

  3. Department of Clinical Genomic Center, Samsung Medical Center, Seoul, Republic of Korea

    Deokgeun Kim

  4. Department of Digital Health, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea

    Deokgeun Kim

  5. Department of Health Sciences and Technology, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea

    Boram Lee & Joon Ho Shim

  6. Samsung Genomic Institute, Samsung Medical Center, Seoul, Republic of Korea

    Boram Lee & Joon Ho Shim

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Contributions

Contribution to design: YLS, YAC. Contribution to analysis and interpretation of the data: YAC, DGK, BL, JHS. YAC and YLS wrote the manuscript. All authors were involved in writing this manuscript and read and approved the final version.

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Correspondence to Yeon-Lim Suh.

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All authors declare no conflicts of interest.

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The Institutional Review Board of Samsung Medical Center approved this study and waived the requirement for informed consent (IRB Number: 2020–04-011).

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No individual patient data were reported in this study.

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Cho, Y.A., Kim, D., Lee, B. et al. Incidence, clinicopathologic, and genetic characteristics of mismatch repair gene-mutated glioblastomas. J Neurooncol 153, 43–53 (2021). https://doi.org/10.1007/s11060-021-03710-0

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  • DOI: https://doi.org/10.1007/s11060-021-03710-0

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