Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel
Rapid technological advances in molecular biology, including next-generation sequencing, have identified key genetic alterations in central nervous system (CNS) tumors. Accordingly, the fifth edition of the World Health Organization (WHO) CNS tumor classification was published in 2021. We analyzed 3...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Japan Neurosurgical Society
2022-09-01
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| Series: | Neurologia Medico-Chirurgica |
| Subjects: | |
| Online Access: | https://www.jstage.jst.go.jp/article/nmc/62/9/62_2022-0103/_pdf/-char/en |
| _version_ | 1817980965254856704 |
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| author | Nayuta HIGA Toshiaki AKAHANE Seiya YOKOYAMA Hajime YONEZAWA Hiroyuki UCHIDA Shingo FUJIO Mari KIRISHIMA Kosuke TAKIGAWA Nobuhiro HATA Keita TOH Junkoh YAMAMOTO Ryosuke HANAYA Akihide TANIMOTO Koji YOSHIMOTO |
| author_facet | Nayuta HIGA Toshiaki AKAHANE Seiya YOKOYAMA Hajime YONEZAWA Hiroyuki UCHIDA Shingo FUJIO Mari KIRISHIMA Kosuke TAKIGAWA Nobuhiro HATA Keita TOH Junkoh YAMAMOTO Ryosuke HANAYA Akihide TANIMOTO Koji YOSHIMOTO |
| author_sort | Nayuta HIGA |
| collection | DOAJ |
| description | Rapid technological advances in molecular biology, including next-generation sequencing, have identified key genetic alterations in central nervous system (CNS) tumors. Accordingly, the fifth edition of the World Health Organization (WHO) CNS tumor classification was published in 2021. We analyzed 303 patients with diffuse glioma using an amplicon-based glioma-tailored gene panel for detecting 1p/19q codeletion and driver gene mutations such as IDH1/2, TERTp, EGFR, and CDKN2A/B on a single platform. Within glioblastomas (GBMs), the most commonly mutated genes were TERTp, TP53, PTEN, NF1, and PDGFRA, which was the most frequently mutated tyrosine kinase receptor in GBM, followed by EGFR. The genes that most commonly showed evidence of loss were PTEN, CDKN2A/B, and RB1, whereas the genes that most commonly showed evidence of gain/amplification were EGFR, PDGFRA, and CDK4. In 22 grade III oligodendroglial tumors, 3 (14%) patients had CDKN2A/B homozygous deletion, and 4 (18%) patients had ARID1A mutation. In grade III oligodendroglial tumors, an ARID1A mutation was associated with worse progression-free survival. Reclassification based on the WHO 2021 classification resulted in 62.5% of grade II/III isocitrate dehydrogenase (IDH)-wildtype astrocytomas being classified as IDH-wildtype GBM and 37.5% as not elsewhere classified. In summary, our glioma-tailored gene panel was applicable for molecular diagnosis in the WHO 2021 classification. In addition, we successfully reclassified the 303 diffuse glioma cases based on the WHO 2021 classification and clarified the genetic profile of diffuse gliomas in the Japanese population. |
| first_indexed | 2024-04-13T22:59:33Z |
| format | Article |
| id | doaj.art-71f1b1a333e64450a6db85d29bf4ba3a |
| institution | Directory Open Access Journal |
| issn | 1349-8029 |
| language | English |
| last_indexed | 2024-04-13T22:59:33Z |
| publishDate | 2022-09-01 |
| publisher | The Japan Neurosurgical Society |
| record_format | Article |
| series | Neurologia Medico-Chirurgica |
| spelling | doaj.art-71f1b1a333e64450a6db85d29bf4ba3a2022-12-22T02:25:53ZengThe Japan Neurosurgical SocietyNeurologia Medico-Chirurgica1349-80292022-09-0162939139910.2176/jns-nmc.2022-01032022-0103Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene PanelNayuta HIGA0Toshiaki AKAHANE1Seiya YOKOYAMA2Hajime YONEZAWA3Hiroyuki UCHIDA4Shingo FUJIO5Mari KIRISHIMA6Kosuke TAKIGAWA7Nobuhiro HATA8Keita TOH9Junkoh YAMAMOTO10Ryosuke HANAYA11Akihide TANIMOTO12Koji YOSHIMOTO13Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityDepartment of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima UniversityDepartment of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima UniversityDepartment of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityDepartment of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityDepartment of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityDepartment of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima UniversityDepartment of Neurosurgery, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Neurosurgery, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Neurosurgery, University of Occupational and Environmental HealthDepartment of Neurosurgery, University of Occupational and Environmental HealthDepartment of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityDepartment of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima UniversityDepartment of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima UniversityRapid technological advances in molecular biology, including next-generation sequencing, have identified key genetic alterations in central nervous system (CNS) tumors. Accordingly, the fifth edition of the World Health Organization (WHO) CNS tumor classification was published in 2021. We analyzed 303 patients with diffuse glioma using an amplicon-based glioma-tailored gene panel for detecting 1p/19q codeletion and driver gene mutations such as IDH1/2, TERTp, EGFR, and CDKN2A/B on a single platform. Within glioblastomas (GBMs), the most commonly mutated genes were TERTp, TP53, PTEN, NF1, and PDGFRA, which was the most frequently mutated tyrosine kinase receptor in GBM, followed by EGFR. The genes that most commonly showed evidence of loss were PTEN, CDKN2A/B, and RB1, whereas the genes that most commonly showed evidence of gain/amplification were EGFR, PDGFRA, and CDK4. In 22 grade III oligodendroglial tumors, 3 (14%) patients had CDKN2A/B homozygous deletion, and 4 (18%) patients had ARID1A mutation. In grade III oligodendroglial tumors, an ARID1A mutation was associated with worse progression-free survival. Reclassification based on the WHO 2021 classification resulted in 62.5% of grade II/III isocitrate dehydrogenase (IDH)-wildtype astrocytomas being classified as IDH-wildtype GBM and 37.5% as not elsewhere classified. In summary, our glioma-tailored gene panel was applicable for molecular diagnosis in the WHO 2021 classification. In addition, we successfully reclassified the 303 diffuse glioma cases based on the WHO 2021 classification and clarified the genetic profile of diffuse gliomas in the Japanese population.https://www.jstage.jst.go.jp/article/nmc/62/9/62_2022-0103/_pdf/-char/engene panelnext-generation sequencingmolecular genetic profilewho 2021 classification |
| spellingShingle | Nayuta HIGA Toshiaki AKAHANE Seiya YOKOYAMA Hajime YONEZAWA Hiroyuki UCHIDA Shingo FUJIO Mari KIRISHIMA Kosuke TAKIGAWA Nobuhiro HATA Keita TOH Junkoh YAMAMOTO Ryosuke HANAYA Akihide TANIMOTO Koji YOSHIMOTO Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel Neurologia Medico-Chirurgica gene panel next-generation sequencing molecular genetic profile who 2021 classification |
| title | Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel |
| title_full | Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel |
| title_fullStr | Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel |
| title_full_unstemmed | Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel |
| title_short | Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel |
| title_sort | molecular genetic profile of 300 japanese patients with diffuse gliomas using a glioma tailored gene panel |
| topic | gene panel next-generation sequencing molecular genetic profile who 2021 classification |
| url | https://www.jstage.jst.go.jp/article/nmc/62/9/62_2022-0103/_pdf/-char/en |
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