Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters

Shunsuke Nakae, Kazuhiro Murayama, Hikaru Sasaki, Masanobu Kumon, Yuya Nishiyama, Shigeo Oba, Kazuhide Adachi, Shinya Nagahisa, Takuro Hayashi, Joji Inamasu, Masato Abe, Mitsuhiro Hasegawa, Yuichi Hirose

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Abstract

Recent progress in neuro-oncology has validated the significance of genetic diagnosis in gliomas. We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas. Furthermore, this analysis had a strong association with patient prognosis. To predict genetic subgroups prior to initial surgery, we retrospectively investigated preoperative radiological data using CT and MRI, including MR spectroscopy (MRS), and evaluated positive 5-aminolevulinic acid (5-ALA) fluorescence as an intraoperative factor. We subsequently compared these factors to differentiate each genetic subgroup. Multiple factors such as age at diagnosis, tumor location, gadolinium enhancement, 5-ALA fluorescence, and several tumor metabolites according to MRS, such as myo-inositol (myo-inositol/total choline) or lipid20, were statistically significant factors for differentiating IDH mutant and wild-type, suggesting that these two subtypes have totally distinct characteristics. In contrast, only calcification, laterality, and lipid13 (lipid13/total Choline) were statistically significant parameters for differentiating TP53 wild-type and mutant in IDH mutant gliomas. In this study, we detected several pre- and intraoperative factors that enabled us to predict genetic subgroups for adult supratentorial gliomas and clarified that lipid13 quantified by MRS is the key tumor metabolite that differentiates TP53 wild-type and mutant in IDH mutant gliomas. These results suggested that each genetic subtype in gliomas selects the distinct lipid synthesis pathways in the process of tumorigenesis.

Original languageEnglish
Pages (from-to)403-412
Number of pages10
JournalJournal of Neuro-Oncology
Volume131
Issue number2
DOIs
Publication statusPublished - 01-01-2017

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Glioma
Aminolevulinic Acid
Magnetic Resonance Spectroscopy
Inositol
Choline
Fluorescence
Neoplasms
Mutation
Gadolinium
Sequence Analysis
Carcinogenesis
Lipids
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Nakae, Shunsuke ; Murayama, Kazuhiro ; Sasaki, Hikaru ; Kumon, Masanobu ; Nishiyama, Yuya ; Oba, Shigeo ; Adachi, Kazuhide ; Nagahisa, Shinya ; Hayashi, Takuro ; Inamasu, Joji ; Abe, Masato ; Hasegawa, Mitsuhiro ; Hirose, Yuichi. / Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters. In: Journal of Neuro-Oncology. 2017 ; Vol. 131, No. 2. pp. 403-412.
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abstract = "Recent progress in neuro-oncology has validated the significance of genetic diagnosis in gliomas. We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas. Furthermore, this analysis had a strong association with patient prognosis. To predict genetic subgroups prior to initial surgery, we retrospectively investigated preoperative radiological data using CT and MRI, including MR spectroscopy (MRS), and evaluated positive 5-aminolevulinic acid (5-ALA) fluorescence as an intraoperative factor. We subsequently compared these factors to differentiate each genetic subgroup. Multiple factors such as age at diagnosis, tumor location, gadolinium enhancement, 5-ALA fluorescence, and several tumor metabolites according to MRS, such as myo-inositol (myo-inositol/total choline) or lipid20, were statistically significant factors for differentiating IDH mutant and wild-type, suggesting that these two subtypes have totally distinct characteristics. In contrast, only calcification, laterality, and lipid13 (lipid13/total Choline) were statistically significant parameters for differentiating TP53 wild-type and mutant in IDH mutant gliomas. In this study, we detected several pre- and intraoperative factors that enabled us to predict genetic subgroups for adult supratentorial gliomas and clarified that lipid13 quantified by MRS is the key tumor metabolite that differentiates TP53 wild-type and mutant in IDH mutant gliomas. These results suggested that each genetic subtype in gliomas selects the distinct lipid synthesis pathways in the process of tumorigenesis.",
author = "Shunsuke Nakae and Kazuhiro Murayama and Hikaru Sasaki and Masanobu Kumon and Yuya Nishiyama and Shigeo Oba and Kazuhide Adachi and Shinya Nagahisa and Takuro Hayashi and Joji Inamasu and Masato Abe and Mitsuhiro Hasegawa and Yuichi Hirose",
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Nakae, S, Murayama, K, Sasaki, H, Kumon, M, Nishiyama, Y, Oba, S, Adachi, K, Nagahisa, S, Hayashi, T, Inamasu, J, Abe, M, Hasegawa, M & Hirose, Y 2017, 'Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters', Journal of Neuro-Oncology, vol. 131, no. 2, pp. 403-412. https://doi.org/10.1007/s11060-016-2313-8

Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters. / Nakae, Shunsuke; Murayama, Kazuhiro; Sasaki, Hikaru; Kumon, Masanobu; Nishiyama, Yuya; Oba, Shigeo; Adachi, Kazuhide; Nagahisa, Shinya; Hayashi, Takuro; Inamasu, Joji; Abe, Masato; Hasegawa, Mitsuhiro; Hirose, Yuichi.

In: Journal of Neuro-Oncology, Vol. 131, No. 2, 01.01.2017, p. 403-412.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters

AU - Nakae, Shunsuke

AU - Murayama, Kazuhiro

AU - Sasaki, Hikaru

AU - Kumon, Masanobu

AU - Nishiyama, Yuya

AU - Oba, Shigeo

AU - Adachi, Kazuhide

AU - Nagahisa, Shinya

AU - Hayashi, Takuro

AU - Inamasu, Joji

AU - Abe, Masato

AU - Hasegawa, Mitsuhiro

AU - Hirose, Yuichi

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Recent progress in neuro-oncology has validated the significance of genetic diagnosis in gliomas. We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas. Furthermore, this analysis had a strong association with patient prognosis. To predict genetic subgroups prior to initial surgery, we retrospectively investigated preoperative radiological data using CT and MRI, including MR spectroscopy (MRS), and evaluated positive 5-aminolevulinic acid (5-ALA) fluorescence as an intraoperative factor. We subsequently compared these factors to differentiate each genetic subgroup. Multiple factors such as age at diagnosis, tumor location, gadolinium enhancement, 5-ALA fluorescence, and several tumor metabolites according to MRS, such as myo-inositol (myo-inositol/total choline) or lipid20, were statistically significant factors for differentiating IDH mutant and wild-type, suggesting that these two subtypes have totally distinct characteristics. In contrast, only calcification, laterality, and lipid13 (lipid13/total Choline) were statistically significant parameters for differentiating TP53 wild-type and mutant in IDH mutant gliomas. In this study, we detected several pre- and intraoperative factors that enabled us to predict genetic subgroups for adult supratentorial gliomas and clarified that lipid13 quantified by MRS is the key tumor metabolite that differentiates TP53 wild-type and mutant in IDH mutant gliomas. These results suggested that each genetic subtype in gliomas selects the distinct lipid synthesis pathways in the process of tumorigenesis.

AB - Recent progress in neuro-oncology has validated the significance of genetic diagnosis in gliomas. We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas. Furthermore, this analysis had a strong association with patient prognosis. To predict genetic subgroups prior to initial surgery, we retrospectively investigated preoperative radiological data using CT and MRI, including MR spectroscopy (MRS), and evaluated positive 5-aminolevulinic acid (5-ALA) fluorescence as an intraoperative factor. We subsequently compared these factors to differentiate each genetic subgroup. Multiple factors such as age at diagnosis, tumor location, gadolinium enhancement, 5-ALA fluorescence, and several tumor metabolites according to MRS, such as myo-inositol (myo-inositol/total choline) or lipid20, were statistically significant factors for differentiating IDH mutant and wild-type, suggesting that these two subtypes have totally distinct characteristics. In contrast, only calcification, laterality, and lipid13 (lipid13/total Choline) were statistically significant parameters for differentiating TP53 wild-type and mutant in IDH mutant gliomas. In this study, we detected several pre- and intraoperative factors that enabled us to predict genetic subgroups for adult supratentorial gliomas and clarified that lipid13 quantified by MRS is the key tumor metabolite that differentiates TP53 wild-type and mutant in IDH mutant gliomas. These results suggested that each genetic subtype in gliomas selects the distinct lipid synthesis pathways in the process of tumorigenesis.

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