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Priority Research Papers:

Remote intracranial recurrence of IDH mutant gliomas is associated with TP53 mutations and an 8q gain

Shunsuke Nakae, Takema Kato, Kazuhiro Murayama, Hikaru Sasaki, Masato Abe, Masanobu Kumon, Tadashi Kumai, Kei Yamashiro, Joji Inamasu, Mitsuhiro Hasegawa, Hiroki Kurahashi and Yuichi Hirose _

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Oncotarget. 2017; 8:84729-84742. https://doi.org/10.18632/oncotarget.20951

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Abstract

Shunsuke Nakae1, Takema Kato2, Kazuhiro Murayama3, Hikaru Sasaki4, Masato Abe5, Masanobu Kumon1, Tadashi Kumai1, Kei Yamashiro1, Joji Inamasu1, Mitsuhiro Hasegawa1, Hiroki Kurahashi2 and Yuichi Hirose1

1 Department of Neurosurgery, Fujita Health University, Toyoake, Japan

2 Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan

3 Department of Radiology, Fujita Health University, Toyoake, Japan

4 Department of Neurosurgery, Keio University, Tokyo, Japan

5 Department of Pathology, Fujita Health University, Toyoake, Japan

Correspondence to:

Yuichi Hirose, email:

Keywords: IDH mutant gliomas, radiological classification for recurrence, Intracranial remote recurrence, TP53 mutations, 8q gain

Received: July 12, 2017 Accepted: August 23, 2017 Published: September 15, 2017

Abstract

Most IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas (N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions. In addition, diffuse tensor imaging suggested that remote intracranial recurrence in the astrocytomas, IDH-mutant with TP53 mutations may occur along major fiber bundles. Remotely recurrent tumors resulted in a higher mortality and significantly harbored an 8q gain; astrocytomas with an 8q gain resulted in significantly shorter overall survival than those without an 8q gain. OncoScan® arrays and next-generation sequencing revealed specific 8q regions (i.e., between 8q22 and 8q24) show a high copy number. In conclusion, only tumors with TP53 mutations showed patterns of remote recurrence in IDH mutant gliomas. Furthermore, an 8q gain was significantly associated with remote intracranial recurrence and can be considered a poor prognostic factor in astrocytomas, IDH-mutant.


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