title: Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters.
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.
authors.affiliation: Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Shunsuke
authors.identifier: 0000-0002-9080-455X
authors.initials: S
authors.lastname: Nakae
authors.affiliation: Department of Radiology, Fujita Health University, Toyoake, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murayama
authors.affiliation: Department of Neurosurgery, Keio University, Tokyo, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kumon
authors.affiliation: Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nishiyama
authors.affiliation: Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohba
authors.affiliation: Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagahisa
authors.affiliation: Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Inamasu
authors.affiliation: Department of Pathology, Fujita Health University, Toyoake, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Neurosurgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. yhirose@fujita-hu.ac.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hirose
mesh_terms: D000328:Adult; D000622:Aminolevulinic Acid / Q000008:administration & dosage; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011182:Postoperative Care; D011300:Preoperative Care; D011524:Protoporphyrins / Q000008:administration & dosage; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D015173:Supratentorial Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D011524:Protoporphyrins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D007521:Isocitrate Dehydrogenase
keywords: Genetic subtypes; Gliomas; MRS; Predictive parameters