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Clinical, histopathological, and molecular analyses of IDH-wild-type WHO grade II–III gliomas to establish genetic predictors of poor prognosis

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Abstract

The genetic features of isocitrate dehydrogenase-wild-type (IDH-wt) lower-grade gliomas (LGGs; World Health Organization grades II and III) are not well defined. This study analyzed the genetic and other features of IDH-wt LGGs to develop a subclassification that can be used to predict their prognosis. Clinical, histopathological, and genetic features of 35 cases of diffuse IDH-wt astrocytoma and IDH-wt anaplastic astrocytoma were analyzed. The following genetic factors were examined: mutations of B-rapidly accelerated fibrosarcoma, telomerase reverse transcriptase promoter (TERTp), histone 3 family 3A, and alpha-thalassemia/mental retardation syndrome, X-linked; and copy number aberrations. In the univariate analysis, the following factors were associated with poor overall survival (OS): the histopathological diagnosis, TERTp mutation, the gain of chromosome 7 (+ 7), and the loss of chromosome 10q (− 10q). In the multivariate analysis, + 7, − 10q, and TERTp mutation were independent prognostic factors associated with poor OS. The median OS was significantly worse for patients who harbored at least one of these factors than for those without any of them (18.5 vs. 54.5 months, P = 0.002). The subclassification of IDH-wt LGGs according to the genetic factors + 7, − 10q, and TERTp mutation is potentially useful for predicting the prognosis.

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Acknowledgements

We also thank Mrs. Fujiko Sueishi and Mrs. Tomoko Suzuki for technical support and Mr. Takeo Ezaki for technical advice.

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Authors and Affiliations

  1. Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan

    Kiyonori Kuwahara, Shigeo Ohba, Shunsuke Nakae, Natsuki Hattori, Mitsuhiro Hasegawa & Yuichi Hirose

  2. Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Eriel Sandika Pareira & Hikaru Sasaki

  3. Department of Diagnostic Pathology, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan

    Seiji Yamada

  4. Department of Pathology, School of Health Sciences, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan

    Masato Abe

Authors
  1. Kiyonori Kuwahara
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  2. Shigeo Ohba
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  3. Shunsuke Nakae
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  4. Natsuki Hattori
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  5. Eriel Sandika Pareira
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  6. Seiji Yamada
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  7. Hikaru Sasaki
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  8. Masato Abe
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  9. Mitsuhiro Hasegawa
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  10. Yuichi Hirose
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Correspondence to Shigeo Ohba.

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Kuwahara, K., Ohba, S., Nakae, S. et al. Clinical, histopathological, and molecular analyses of IDH-wild-type WHO grade II–III gliomas to establish genetic predictors of poor prognosis. Brain Tumor Pathol 36, 135–143 (2019). https://doi.org/10.1007/s10014-019-00348-9

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  • DOI: https://doi.org/10.1007/s10014-019-00348-9

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