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MURAGAKI Yoshihiro
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Visiting Professor |
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| Article types | Other |
| Language | English |
| Peer review | Non peer reviewed |
| Title | Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. |
| Journal | Formal name：Neuro-oncology Abbreviation：Neuro Oncol ISSN code：15235866/15228517 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 20(1),pp.66-77 |
| Author and coauthor | AOKI Kosuke†, NAKAMURA Hideo, SUZUKI Hiromichi, MATSUO Keitaro, KATAOKA Keisuke, SHIMAMURA Teppei, MOTOMURA Kazuya, OHKA Fumiharu, SHIINA Satoshi, YAMAMOTO Takashi, NAGATA Yasunobu, YOSHIZATO Tetsuichi, MIZOGUCHI Masahiro, ABE Tatsuya, MOMII Yasutomo, MURAGAKI Yoshihiro, WATANABE Reiko, ITO Ichiro, SANADA Masashi, YAJIMA Hironori, MORITA Naoya, TAKEUCHI Ichiro, MIYANO Satoru, WAKABAYASHI Toshihiko, OGAWA Seishi, NATSUME Atsushi |
| Publication date | 2018/01 |
| Summary | Background:Diffuse lower-grade gliomas (LGGs) are genetically classified into 3 distinct subtypes based on isocitrate dehydrogenase (IDH) mutation status and codeletion of chromosome 1p and 19q (1p/19q). However, the subtype-specific effects of additional genetic lesions on survival are largely unknown.Methods:Using Cox proportional hazards regression modeling, we investigated the subtype-specific effects of genetic alterations and clinicopathological factors on survival in each LGG subtype, in a Japanese cohort of LGG cases fully genotyped for driver mutations and copy number variations associated with LGGs (n = 308). The results were validated using a dataset from 414 LGG cases available from The Cancer Genome Atlas (TCGA).Results:In Oligodendroglioma, IDH-mutant and 1p/19q codeleted, NOTCH1 mutations (P = 0.0041) and incomplete resection (P = 0.0019) were significantly associated with shorter survival. In Astrocytoma, IDH-mutant, PIK3R1 mutations (P = 0.0014) and altered retinoblastoma pathway genes (RB1, CDKN2A, and CDK4) (P = 0.013) were independent predictors of poor survival. In IDH-wildtype LGGs, co-occurrence of 7p gain, 10q loss, mutation in the TERT promoter (P = 0.024), and grade III histology (P<0.0001) independently predicted poor survival. IDH-wildtype LGGs without any of these factors were diagnosed at a younger age (P = 0.042), and were less likely to have genetic lesions characteristic of glioblastoma, in comparison with other IDH-wildtype LGGs, suggesting that they likely represented biologically different subtypes. These results were largely confirmed in the cohort of TCGA.Conclusions:Subtype-specific genetic lesions can be used to stratify patients within each LGGsubtype. enabling better prognostication and management. |
| DOI | 10.1093/neuonc/nox132 |
| PMID | 29016839 |