TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations
TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-muta...
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| creator | Arita, Hideyuki Matsushita, Yuko Machida, Ryunosuke Yamasaki, Kai Hata, Nobuhiro Ohno, Makoto Yamaguchi, Shigeru Sasayama, Takashi Tanaka, Shota Higuchi, Fumi Iuchi, Toshihiko Saito, Kuniaki Kanamori, Masayuki Matsuda, Ken-Ichiro Miyake, Yohei Tamura, Kaoru Tamai, Sho Nakamura, Taishi Uda, Takehiro Okita, Yoshiko Fukai, Junya Sakamoto, Daisuke Hattori, Yasuhiko Pareira, Eriel Sandika Hatae, Ryusuke Ishi, Yukitomo Miyakita, Yasuji Tanaka, Kazuhiro Takayanagi, Shunsaku Otani, Ryohei Sakaida, Tsukasa Kobayashi, Keiichi Saito, Ryuta Kurozumi, Kazuhiko Shofuda, Tomoko Nonaka, Masahiro Suzuki, Hiroyoshi Shibuya, Makoto Komori, Takashi Sasaki, Hikaru Mizoguchi, Masahiro Kishima, Haruhiko Nakada, Mitsutoshi Sonoda, Yukihiko Tominaga, Teiji Nagane, Motoo Nishikawa, Ryo Kanemura, Yonehiro Kuchiba, Aya Narita, Yoshitaka Ichimura, Koichi |
| description | TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p |
| doi_str_mv | 10.1186/s40478-020-01078-2 |
| format | Article |
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However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.</description><identifier>ISSN: 2051-5960</identifier><identifier>EISSN: 2051-5960</identifier><identifier>DOI: 10.1186/s40478-020-01078-2</identifier><identifier>PMID: 33228806</identifier><language>eng</language><publisher>England: BioMed Central</publisher><subject>Adolescent ; Adult ; Age ; Aged ; Aged, 80 and over ; Astrocytoma - genetics ; Astrocytoma - pathology ; Astrocytoma - therapy ; Brain cancer ; Brain Neoplasms - genetics ; Brain Neoplasms - pathology ; Brain Neoplasms - therapy ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 19 ; Female ; Glioblastoma - genetics ; Glioblastoma - pathology ; Glioblastoma - therapy ; Glioma ; Glioma - genetics ; Glioma - pathology ; Glioma - therapy ; Histology ; Humans ; Isocitrate Dehydrogenase - genetics ; Karnofsky Performance Status ; Male ; Medical prognosis ; Middle Aged ; Multivariate Analysis ; Mutation ; Neoplasm Grading ; Neurosurgical Procedures ; Oligodendroglioma - genetics ; Oligodendroglioma - pathology ; Oligodendroglioma - therapy ; Patients ; Prognosis ; Promoter Regions, Genetic - genetics ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Retrospective Studies ; Surgery ; Survival analysis ; Survival Rate ; Telomerase - genetics ; Tumors ; Young Adult</subject><ispartof>Acta neuropathologica communications, 2020-11, Vol.8 (1), p.201-201, Article 201</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-9ede28a25c12fd5d57f0e7e94a5f07e9e0d4620a473c102dd52b57da0e1d5003</citedby><cites>FETCH-LOGICAL-c430t-9ede28a25c12fd5d57f0e7e94a5f07e9e0d4620a473c102dd52b57da0e1d5003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685625/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685625/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33228806$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arita, Hideyuki</creatorcontrib><creatorcontrib>Matsushita, Yuko</creatorcontrib><creatorcontrib>Machida, Ryunosuke</creatorcontrib><creatorcontrib>Yamasaki, Kai</creatorcontrib><creatorcontrib>Hata, Nobuhiro</creatorcontrib><creatorcontrib>Ohno, Makoto</creatorcontrib><creatorcontrib>Yamaguchi, Shigeru</creatorcontrib><creatorcontrib>Sasayama, Takashi</creatorcontrib><creatorcontrib>Tanaka, Shota</creatorcontrib><creatorcontrib>Higuchi, Fumi</creatorcontrib><creatorcontrib>Iuchi, Toshihiko</creatorcontrib><creatorcontrib>Saito, Kuniaki</creatorcontrib><creatorcontrib>Kanamori, Masayuki</creatorcontrib><creatorcontrib>Matsuda, Ken-Ichiro</creatorcontrib><creatorcontrib>Miyake, Yohei</creatorcontrib><creatorcontrib>Tamura, Kaoru</creatorcontrib><creatorcontrib>Tamai, Sho</creatorcontrib><creatorcontrib>Nakamura, Taishi</creatorcontrib><creatorcontrib>Uda, Takehiro</creatorcontrib><creatorcontrib>Okita, Yoshiko</creatorcontrib><creatorcontrib>Fukai, Junya</creatorcontrib><creatorcontrib>Sakamoto, Daisuke</creatorcontrib><creatorcontrib>Hattori, Yasuhiko</creatorcontrib><creatorcontrib>Pareira, Eriel Sandika</creatorcontrib><creatorcontrib>Hatae, Ryusuke</creatorcontrib><creatorcontrib>Ishi, Yukitomo</creatorcontrib><creatorcontrib>Miyakita, Yasuji</creatorcontrib><creatorcontrib>Tanaka, Kazuhiro</creatorcontrib><creatorcontrib>Takayanagi, Shunsaku</creatorcontrib><creatorcontrib>Otani, Ryohei</creatorcontrib><creatorcontrib>Sakaida, Tsukasa</creatorcontrib><creatorcontrib>Kobayashi, Keiichi</creatorcontrib><creatorcontrib>Saito, Ryuta</creatorcontrib><creatorcontrib>Kurozumi, Kazuhiko</creatorcontrib><creatorcontrib>Shofuda, Tomoko</creatorcontrib><creatorcontrib>Nonaka, Masahiro</creatorcontrib><creatorcontrib>Suzuki, Hiroyoshi</creatorcontrib><creatorcontrib>Shibuya, Makoto</creatorcontrib><creatorcontrib>Komori, Takashi</creatorcontrib><creatorcontrib>Sasaki, Hikaru</creatorcontrib><creatorcontrib>Mizoguchi, Masahiro</creatorcontrib><creatorcontrib>Kishima, Haruhiko</creatorcontrib><creatorcontrib>Nakada, Mitsutoshi</creatorcontrib><creatorcontrib>Sonoda, Yukihiko</creatorcontrib><creatorcontrib>Tominaga, Teiji</creatorcontrib><creatorcontrib>Nagane, Motoo</creatorcontrib><creatorcontrib>Nishikawa, Ryo</creatorcontrib><creatorcontrib>Kanemura, Yonehiro</creatorcontrib><creatorcontrib>Kuchiba, Aya</creatorcontrib><creatorcontrib>Narita, Yoshitaka</creatorcontrib><creatorcontrib>Ichimura, Koichi</creatorcontrib><title>TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations</title><title>Acta neuropathologica communications</title><addtitle>Acta Neuropathol Commun</addtitle><description>TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Astrocytoma - genetics</subject><subject>Astrocytoma - pathology</subject><subject>Astrocytoma - therapy</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain Neoplasms - therapy</subject><subject>Chromosome Deletion</subject><subject>Chromosomes, Human, Pair 1</subject><subject>Chromosomes, Human, Pair 19</subject><subject>Female</subject><subject>Glioblastoma - genetics</subject><subject>Glioblastoma - pathology</subject><subject>Glioblastoma - therapy</subject><subject>Glioma</subject><subject>Glioma - genetics</subject><subject>Glioma - pathology</subject><subject>Glioma - therapy</subject><subject>Histology</subject><subject>Humans</subject><subject>Isocitrate Dehydrogenase - genetics</subject><subject>Karnofsky Performance Status</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Mutation</subject><subject>Neoplasm Grading</subject><subject>Neurosurgical Procedures</subject><subject>Oligodendroglioma - genetics</subject><subject>Oligodendroglioma - pathology</subject><subject>Oligodendroglioma - therapy</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Proportional Hazards Models</subject><subject>Radiotherapy, Adjuvant</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><subject>Survival analysis</subject><subject>Survival Rate</subject><subject>Telomerase - genetics</subject><subject>Tumors</subject><subject>Young 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Shota ; Higuchi, Fumi ; Iuchi, Toshihiko ; Saito, Kuniaki ; Kanamori, Masayuki ; Matsuda, Ken-Ichiro ; Miyake, Yohei ; Tamura, Kaoru ; Tamai, Sho ; Nakamura, Taishi ; Uda, Takehiro ; Okita, Yoshiko ; Fukai, Junya ; Sakamoto, Daisuke ; Hattori, Yasuhiko ; Pareira, Eriel Sandika ; Hatae, Ryusuke ; Ishi, Yukitomo ; Miyakita, Yasuji ; Tanaka, Kazuhiro ; Takayanagi, Shunsaku ; Otani, Ryohei ; Sakaida, Tsukasa ; Kobayashi, Keiichi ; Saito, Ryuta ; Kurozumi, Kazuhiko ; Shofuda, Tomoko ; Nonaka, Masahiro ; Suzuki, Hiroyoshi ; Shibuya, Makoto ; Komori, Takashi ; Sasaki, Hikaru ; Mizoguchi, Masahiro ; Kishima, Haruhiko ; Nakada, Mitsutoshi ; Sonoda, Yukihiko ; Tominaga, Teiji ; Nagane, Motoo ; Nishikawa, Ryo ; Kanemura, Yonehiro ; Kuchiba, Aya ; Narita, Yoshitaka ; Ichimura, Koichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-9ede28a25c12fd5d57f0e7e94a5f07e9e0d4620a473c102dd52b57da0e1d5003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Astrocytoma - genetics</topic><topic>Astrocytoma - pathology</topic><topic>Astrocytoma - therapy</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain Neoplasms - therapy</topic><topic>Chromosome Deletion</topic><topic>Chromosomes, Human, Pair 1</topic><topic>Chromosomes, Human, Pair 19</topic><topic>Female</topic><topic>Glioblastoma - genetics</topic><topic>Glioblastoma - pathology</topic><topic>Glioblastoma - therapy</topic><topic>Glioma</topic><topic>Glioma - genetics</topic><topic>Glioma - pathology</topic><topic>Glioma - therapy</topic><topic>Histology</topic><topic>Humans</topic><topic>Isocitrate Dehydrogenase - genetics</topic><topic>Karnofsky Performance Status</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Mutation</topic><topic>Neoplasm Grading</topic><topic>Neurosurgical Procedures</topic><topic>Oligodendroglioma - genetics</topic><topic>Oligodendroglioma - pathology</topic><topic>Oligodendroglioma - therapy</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Proportional Hazards Models</topic><topic>Radiotherapy, Adjuvant</topic><topic>Retrospective Studies</topic><topic>Surgery</topic><topic>Survival analysis</topic><topic>Survival Rate</topic><topic>Telomerase - genetics</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arita, Hideyuki</creatorcontrib><creatorcontrib>Matsushita, Yuko</creatorcontrib><creatorcontrib>Machida, Ryunosuke</creatorcontrib><creatorcontrib>Yamasaki, Kai</creatorcontrib><creatorcontrib>Hata, Nobuhiro</creatorcontrib><creatorcontrib>Ohno, Makoto</creatorcontrib><creatorcontrib>Yamaguchi, Shigeru</creatorcontrib><creatorcontrib>Sasayama, Takashi</creatorcontrib><creatorcontrib>Tanaka, Shota</creatorcontrib><creatorcontrib>Higuchi, Fumi</creatorcontrib><creatorcontrib>Iuchi, Toshihiko</creatorcontrib><creatorcontrib>Saito, Kuniaki</creatorcontrib><creatorcontrib>Kanamori, Masayuki</creatorcontrib><creatorcontrib>Matsuda, Ken-Ichiro</creatorcontrib><creatorcontrib>Miyake, Yohei</creatorcontrib><creatorcontrib>Tamura, Kaoru</creatorcontrib><creatorcontrib>Tamai, Sho</creatorcontrib><creatorcontrib>Nakamura, Taishi</creatorcontrib><creatorcontrib>Uda, Takehiro</creatorcontrib><creatorcontrib>Okita, Yoshiko</creatorcontrib><creatorcontrib>Fukai, Junya</creatorcontrib><creatorcontrib>Sakamoto, Daisuke</creatorcontrib><creatorcontrib>Hattori, Yasuhiko</creatorcontrib><creatorcontrib>Pareira, Eriel Sandika</creatorcontrib><creatorcontrib>Hatae, Ryusuke</creatorcontrib><creatorcontrib>Ishi, Yukitomo</creatorcontrib><creatorcontrib>Miyakita, Yasuji</creatorcontrib><creatorcontrib>Tanaka, Kazuhiro</creatorcontrib><creatorcontrib>Takayanagi, Shunsaku</creatorcontrib><creatorcontrib>Otani, Ryohei</creatorcontrib><creatorcontrib>Sakaida, Tsukasa</creatorcontrib><creatorcontrib>Kobayashi, Keiichi</creatorcontrib><creatorcontrib>Saito, Ryuta</creatorcontrib><creatorcontrib>Kurozumi, Kazuhiko</creatorcontrib><creatorcontrib>Shofuda, Tomoko</creatorcontrib><creatorcontrib>Nonaka, Masahiro</creatorcontrib><creatorcontrib>Suzuki, Hiroyoshi</creatorcontrib><creatorcontrib>Shibuya, Makoto</creatorcontrib><creatorcontrib>Komori, Takashi</creatorcontrib><creatorcontrib>Sasaki, Hikaru</creatorcontrib><creatorcontrib>Mizoguchi, Masahiro</creatorcontrib><creatorcontrib>Kishima, Haruhiko</creatorcontrib><creatorcontrib>Nakada, Mitsutoshi</creatorcontrib><creatorcontrib>Sonoda, Yukihiko</creatorcontrib><creatorcontrib>Tominaga, Teiji</creatorcontrib><creatorcontrib>Nagane, Motoo</creatorcontrib><creatorcontrib>Nishikawa, Ryo</creatorcontrib><creatorcontrib>Kanemura, Yonehiro</creatorcontrib><creatorcontrib>Kuchiba, Aya</creatorcontrib><creatorcontrib>Narita, Yoshitaka</creatorcontrib><creatorcontrib>Ichimura, Koichi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta neuropathologica communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arita, Hideyuki</au><au>Matsushita, Yuko</au><au>Machida, Ryunosuke</au><au>Yamasaki, Kai</au><au>Hata, Nobuhiro</au><au>Ohno, Makoto</au><au>Yamaguchi, Shigeru</au><au>Sasayama, Takashi</au><au>Tanaka, Shota</au><au>Higuchi, Fumi</au><au>Iuchi, Toshihiko</au><au>Saito, Kuniaki</au><au>Kanamori, Masayuki</au><au>Matsuda, Ken-Ichiro</au><au>Miyake, Yohei</au><au>Tamura, Kaoru</au><au>Tamai, Sho</au><au>Nakamura, Taishi</au><au>Uda, Takehiro</au><au>Okita, Yoshiko</au><au>Fukai, Junya</au><au>Sakamoto, Daisuke</au><au>Hattori, Yasuhiko</au><au>Pareira, Eriel Sandika</au><au>Hatae, Ryusuke</au><au>Ishi, Yukitomo</au><au>Miyakita, Yasuji</au><au>Tanaka, Kazuhiro</au><au>Takayanagi, Shunsaku</au><au>Otani, Ryohei</au><au>Sakaida, Tsukasa</au><au>Kobayashi, Keiichi</au><au>Saito, Ryuta</au><au>Kurozumi, Kazuhiko</au><au>Shofuda, Tomoko</au><au>Nonaka, Masahiro</au><au>Suzuki, Hiroyoshi</au><au>Shibuya, Makoto</au><au>Komori, Takashi</au><au>Sasaki, Hikaru</au><au>Mizoguchi, Masahiro</au><au>Kishima, Haruhiko</au><au>Nakada, Mitsutoshi</au><au>Sonoda, Yukihiko</au><au>Tominaga, Teiji</au><au>Nagane, Motoo</au><au>Nishikawa, Ryo</au><au>Kanemura, Yonehiro</au><au>Kuchiba, Aya</au><au>Narita, Yoshitaka</au><au>Ichimura, Koichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations</atitle><jtitle>Acta neuropathologica communications</jtitle><addtitle>Acta Neuropathol Commun</addtitle><date>2020-11-23</date><risdate>2020</risdate><volume>8</volume><issue>1</issue><spage>201</spage><epage>201</epage><pages>201-201</pages><artnum>201</artnum><issn>2051-5960</issn><eissn>2051-5960</eissn><abstract>TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.</abstract><cop>England</cop><pub>BioMed Central</pub><pmid>33228806</pmid><doi>10.1186/s40478-020-01078-2</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2051-5960 |
| ispartof | Acta neuropathologica communications, 2020-11, Vol.8 (1), p.201-201, Article 201 |
| issn | 2051-5960 2051-5960 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7685625 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; SpringerNature Journals; PubMed Central Open Access; Springer Nature OA Free Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adolescent Adult Age Aged Aged, 80 and over Astrocytoma - genetics Astrocytoma - pathology Astrocytoma - therapy Brain cancer Brain Neoplasms - genetics Brain Neoplasms - pathology Brain Neoplasms - therapy Chromosome Deletion Chromosomes, Human, Pair 1 Chromosomes, Human, Pair 19 Female Glioblastoma - genetics Glioblastoma - pathology Glioblastoma - therapy Glioma Glioma - genetics Glioma - pathology Glioma - therapy Histology Humans Isocitrate Dehydrogenase - genetics Karnofsky Performance Status Male Medical prognosis Middle Aged Multivariate Analysis Mutation Neoplasm Grading Neurosurgical Procedures Oligodendroglioma - genetics Oligodendroglioma - pathology Oligodendroglioma - therapy Patients Prognosis Promoter Regions, Genetic - genetics Proportional Hazards Models Radiotherapy, Adjuvant Retrospective Studies Surgery Survival analysis Survival Rate Telomerase - genetics Tumors Young Adult |
| title | TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T11%3A03%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=TERT%20promoter%20mutation%20confers%20favorable%20prognosis%20regardless%20of%201p/19q%20status%20in%20adult%20diffuse%20gliomas%20with%20IDH1/2%20mutations&rft.jtitle=Acta%20neuropathologica%20communications&rft.au=Arita,%20Hideyuki&rft.date=2020-11-23&rft.volume=8&rft.issue=1&rft.spage=201&rft.epage=201&rft.pages=201-201&rft.artnum=201&rft.issn=2051-5960&rft.eissn=2051-5960&rft_id=info:doi/10.1186/s40478-020-01078-2&rft_dat=%3Cproquest_pubme%3E2464149927%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2471116204&rft_id=info:pmid/33228806&rfr_iscdi=true |