Prognostic relevance of genetic alterations in diffuse lower-grade gliomas

Kosuke Aoki, Hideo Nakamura, Hiromichi Suzuki, Keitaro Matsuo, Keisuke Kataoka, Teppei Shimamura, Kazuya Motomura, Fumiharu Ohka, Satoshi Shiina, Takashi Yamamoto, Yasunobu Nagata, Tetsuichi Yoshizato, Masahiro Mizoguchi, Tatsuya Abe, Yasutomo Momii, Yoshihiro Muragaki, Reiko Watanabe, Ichiro Ito, Masashi Sanada, Hironori YajimaNaoya Morita, Ichiro Takeuchi, Satoru Miyano, Toshihiko Wakabayashi, Seishi Ogawa, Atsushi Natsume

研究成果: ジャーナルへの寄稿記事

30 引用 (Scopus)

抄録

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 LGG subtype. enabling better prognostication and management.

元の言語英語
ページ(範囲)66-77
ページ数12
ジャーナルNeuro-Oncology
20
発行部数1
DOI
出版物ステータス出版済み - 1 1 2018

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Glioma
Isocitrate Dehydrogenase
Mutation
Survival
Atlases
Genome
Retinoblastoma Genes
Oligodendroglioma
Astrocytoma
Glioblastoma
Neoplasms
Histology
Chromosomes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

これを引用

Aoki, K., Nakamura, H., Suzuki, H., Matsuo, K., Kataoka, K., Shimamura, T., ... Natsume, A. (2018). Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. Neuro-Oncology, 20(1), 66-77. https://doi.org/10.1093/neuonc/nox132

Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. / 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.

:: Neuro-Oncology, 巻 20, 番号 1, 01.01.2018, p. 66-77.

研究成果: ジャーナルへの寄稿記事

Aoki, K, Nakamura, H, Suzuki, H, Matsuo, K, Kataoka, K, Shimamura, T, Motomura, K, Ohka, F, Shiina, S, Yamamoto, T, Nagata, Y, Yoshizato, T, Mizoguchi, M, Abe, T, Momii, Y, Muragaki, Y, Watanabe, R, Ito, I, Sanada, M, Yajima, H, Morita, N, Takeuchi, I, Miyano, S, Wakabayashi, T, Ogawa, S & Natsume, A 2018, 'Prognostic relevance of genetic alterations in diffuse lower-grade gliomas', Neuro-Oncology, 巻. 20, 番号 1, pp. 66-77. https://doi.org/10.1093/neuonc/nox132
Aoki K, Nakamura H, Suzuki H, Matsuo K, Kataoka K, Shimamura T その他. Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. Neuro-Oncology. 2018 1 1;20(1):66-77. https://doi.org/10.1093/neuonc/nox132
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. / Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. :: Neuro-Oncology. 2018 ; 巻 20, 番号 1. pp. 66-77.
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abstract = "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 LGG subtype. enabling better prognostication and management.",
author = "Kosuke Aoki and Hideo Nakamura and Hiromichi Suzuki and Keitaro Matsuo and Keisuke Kataoka and Teppei Shimamura and Kazuya Motomura and Fumiharu Ohka and Satoshi Shiina and Takashi Yamamoto and Yasunobu Nagata and Tetsuichi Yoshizato and Masahiro Mizoguchi and Tatsuya Abe and Yasutomo Momii and Yoshihiro Muragaki and Reiko Watanabe and Ichiro Ito and Masashi Sanada and Hironori Yajima and Naoya Morita and Ichiro Takeuchi and Satoru Miyano and Toshihiko Wakabayashi and Seishi Ogawa and Atsushi Natsume",
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T1 - Prognostic relevance of genetic alterations in diffuse lower-grade gliomas

AU - Aoki, Kosuke

AU - Nakamura, Hideo

AU - Suzuki, Hiromichi

AU - Matsuo, Keitaro

AU - Kataoka, Keisuke

AU - Shimamura, Teppei

AU - Motomura, Kazuya

AU - Ohka, Fumiharu

AU - Shiina, Satoshi

AU - Yamamoto, Takashi

AU - Nagata, Yasunobu

AU - Yoshizato, Tetsuichi

AU - Mizoguchi, Masahiro

AU - Abe, Tatsuya

AU - Momii, Yasutomo

AU - Muragaki, Yoshihiro

AU - Watanabe, Reiko

AU - Ito, Ichiro

AU - Sanada, Masashi

AU - Yajima, Hironori

AU - Morita, Naoya

AU - Takeuchi, Ichiro

AU - Miyano, Satoru

AU - Wakabayashi, Toshihiko

AU - Ogawa, Seishi

AU - Natsume, Atsushi

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 LGG subtype. enabling better prognostication and management.

AB - 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 LGG subtype. enabling better prognostication and management.

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