PCR-based simple subgrouping is validated for classification of gliomas and defines negative prognostic copy number aberrations in IDH mutant gliomas

Shunsuke Nakae, Hikaru Sasaki, Saeko Hayashi, Natsuki Hattori, Masanobu Kumon, Yuya Nishiyama, Kazuhide Adachi, Shinya Nagahisa, Takuro Hayashi, Joji Inamasu, Masato Abe, Mitsuhiro Hasegawa, Yuichi Hirose

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6 Citations (Scopus)

Abstract

Genetic subgrouping of gliomas has been emphasized recently, particularly after the finding of isocitrate dehydrogenase 1 (IDH1) mutations. In a previous study, we investigated whole-chromosome copy number aberrations (CNAs) of gliomas and have described genetic subgrouping based on CNAs and IDH1 mutations. Subsequently, we classified gliomas using simple polymerase chain reaction (PCR)-based methods to improve the availability of genetic subgrouping. We selected IDH1/2 and TP53 as markers and analyzed 237 adult supratentorial gliomas using Sanger sequencing. Using these markers, we classified gliomas into three subgroups that were strongly associated with patient prognoses. These included IDH mutant gliomas without TP53 mutations, IDH mutant gliomas with TP53 mutations, and IDH wild-type gliomas. IDH mutant gliomas without TP53 mutations, which mostly corresponded to gliomas carrying 1p19q co-deletions, showed lower recurrence rates than the other 2 groups. In the other high-recurrence groups, the median progressionfree survival (PFS) and overall survival (OS) of patients with IDH mutant gliomas with TP53 mutations were significantly longer than those of patients with IDH wild-type gliomas. Notably, most IDH mutant gliomas with TP53 mutations had at least one of the CNAs +7q, +8q, -9p, and -11p. Moreover, IDH mutant gliomas with at least one of these CNAs had a significantly worse prognosis than did other IDH mutant gliomas. PCR-based mutation analyses of IDH and TP53 were sufficient for simple genetic diagnosis of glioma that were strongly associated with prognosis of patients and enabled us to detect negative CNAs in IDH mutant gliomas.

Original languageEnglish
Article numbere0142750
JournalPloS one
Volume10
Issue number11
DOIs
Publication statusPublished - 2015 Nov 1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Nakae, S., Sasaki, H., Hayashi, S., Hattori, N., Kumon, M., Nishiyama, Y., Adachi, K., Nagahisa, S., Hayashi, T., Inamasu, J., Abe, M., Hasegawa, M., & Hirose, Y. (2015). PCR-based simple subgrouping is validated for classification of gliomas and defines negative prognostic copy number aberrations in IDH mutant gliomas. PloS one, 10(11), [e0142750]. https://doi.org/10.1371/journal.pone.0142750