title: World Health Organization grade II-III astrocytomas consist of genetically distinct tumor lineages.
abstract: Recent investigations revealed genetic analysis provides important information in management of gliomas, and we previously reported grade II-III gliomas could be classified into clinically relevant subgroups based on the DNA copy number aberrations (CNAs). To develop more precise genetic subgrouping, we investigated the correlation between CNAs and mutational status of the gene encoding isocitrate dehydrogenase (IDH) of those tumors. We analyzed the IDH status and CNAs of 174 adult supratentorial gliomas of astrocytic or oligodendroglial origin by PCR-based direct sequencing and comparative genomic hybridization, respectively. We analyzed the relationship between genetic subclassification and clinical features. We found the most frequent aberrations in IDH mutant tumors were the combined whole arm-loss of 1p and 19q (1p/19q codeletion) followed by gain on chromosome arm 7q (+7q). The gain of whole chromosome 7 (+7) and loss of 10q (-10q) were detected in IDH wild-type tumors. Kaplan-Meier estimates for progression-free survival showed that the tumors with mutant IDH, -1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wild-type IDH, +7, or -10q. As tumors with +7 (IDH wild-type) showed a more aggressive clinical nature, they are probably not a subtype that developed from the slowly progressive tumors with +7q (IDH mutant). Thus, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management.
authors.affiliation: Department of Neurosurgery, Fujita Health University, Toyoake, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Neurosurgery, Fujita Health University, Toyoake, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hirose
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Neurosurgery, Fujita Health University, Toyoake, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nakae
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Neurosurgery, Fujita Health University, Toyoake, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohba
authors.affiliation: Department of Neurosurgery, Fujita Health University, Toyoake, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Department of Neurosurgery, Fujita Health University, Toyoake, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Neurosurgery, Fujita Health University, Toyoake, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nishiyama
authors.affiliation: Department of Neurosurgery, Fujita Health University, Toyoake, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Faculty of Medical Technology, Fujita Health University, Toyoake, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Abe
mesh_terms: D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology*; D019070:Cell Lineage / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D018450:Disease Progression; D052138:Genes, Neoplasm; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D014944:World Health Organization
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: Astrocytomas; DNA copy number; IDH; chromosome 7; genetic subgrouping