Prognostic stratification for IDH-wild-type lower-grade astrocytoma by Sanger sequencing and copy-number alteration analysis with MLPA

Abstract The characteristics of IDH-wild-type lower-grade astrocytoma remain unclear. According to cIMPACT-NOW update 3, IDH-wild-type astrocytomas with any of the following factors show poor prognosis: combination of chromosome 7 gain and 10 loss (+ 7/− 10), and/or EGFR amplification, and/or TERT p...

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Autores principales:	Yasuhide Makino, Yoshiki Arakawa, Ema Yoshioka, Tomoko Shofuda, Takeshi Kawauchi, Yukinori Terada, Masahiro Tanji, Daisuke Kanematsu, Yohei Mineharu, Susumu Miyamoto, Yonehiro Kanemura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/270c73917d924678a3734d63e82fb512
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spelling	oai:doaj.org-article:270c73917d924678a3734d63e82fb5122021-12-02T16:08:05ZPrognostic stratification for IDH-wild-type lower-grade astrocytoma by Sanger sequencing and copy-number alteration analysis with MLPA10.1038/s41598-021-93937-82045-2322https://doaj.org/article/270c73917d924678a3734d63e82fb5122021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93937-8https://doaj.org/toc/2045-2322Abstract The characteristics of IDH-wild-type lower-grade astrocytoma remain unclear. According to cIMPACT-NOW update 3, IDH-wild-type astrocytomas with any of the following factors show poor prognosis: combination of chromosome 7 gain and 10 loss (+ 7/− 10), and/or EGFR amplification, and/or TERT promoter (TERTp) mutation. Multiplex ligation-dependent probe amplification (MLPA) can detect copy number alterations at reasonable cost. The purpose of this study was to identify a precise, cost-effective method for stratifying the prognosis of IDH-wild-type astrocytoma. Sanger sequencing, MLPA, and quantitative methylation-specific PCR were performed for 42 IDH-wild-type lower-grade astrocytomas surgically treated at Kyoto University Hospital, and overall survival was analysed for 40 patients who underwent first surgery. Of the 42 IDH-wild-type astrocytomas, 21 were classified as grade 4 using cIMPACT-NOW update 3 criteria and all had either TERTp mutation or EGFR amplification. Kaplan–Meier analysis confirmed the prognostic significance of cIMPACT-NOW criteria, and World Health Organization grade was also prognostic. Cox regression hazard model identified independent significant prognostic indicators of PTEN loss (risk ratio, 9.75; p < 0.001) and PDGFRA amplification (risk ratio, 13.9; p = 0.002). The classification recommended by cIMPACT-NOW update 3 could be completed using Sanger sequencing and MLPA. Survival analysis revealed PTEN and PDGFRA were significant prognostic factors for IDH-wild-type lower-grade astrocytoma.Yasuhide MakinoYoshiki ArakawaEma YoshiokaTomoko ShofudaTakeshi KawauchiYukinori TeradaMasahiro TanjiDaisuke KanematsuYohei MineharuSusumu MiyamotoYonehiro KanemuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yasuhide Makino Yoshiki Arakawa Ema Yoshioka Tomoko Shofuda Takeshi Kawauchi Yukinori Terada Masahiro Tanji Daisuke Kanematsu Yohei Mineharu Susumu Miyamoto Yonehiro Kanemura Prognostic stratification for IDH-wild-type lower-grade astrocytoma by Sanger sequencing and copy-number alteration analysis with MLPA
description	Abstract The characteristics of IDH-wild-type lower-grade astrocytoma remain unclear. According to cIMPACT-NOW update 3, IDH-wild-type astrocytomas with any of the following factors show poor prognosis: combination of chromosome 7 gain and 10 loss (+ 7/− 10), and/or EGFR amplification, and/or TERT promoter (TERTp) mutation. Multiplex ligation-dependent probe amplification (MLPA) can detect copy number alterations at reasonable cost. The purpose of this study was to identify a precise, cost-effective method for stratifying the prognosis of IDH-wild-type astrocytoma. Sanger sequencing, MLPA, and quantitative methylation-specific PCR were performed for 42 IDH-wild-type lower-grade astrocytomas surgically treated at Kyoto University Hospital, and overall survival was analysed for 40 patients who underwent first surgery. Of the 42 IDH-wild-type astrocytomas, 21 were classified as grade 4 using cIMPACT-NOW update 3 criteria and all had either TERTp mutation or EGFR amplification. Kaplan–Meier analysis confirmed the prognostic significance of cIMPACT-NOW criteria, and World Health Organization grade was also prognostic. Cox regression hazard model identified independent significant prognostic indicators of PTEN loss (risk ratio, 9.75; p < 0.001) and PDGFRA amplification (risk ratio, 13.9; p = 0.002). The classification recommended by cIMPACT-NOW update 3 could be completed using Sanger sequencing and MLPA. Survival analysis revealed PTEN and PDGFRA were significant prognostic factors for IDH-wild-type lower-grade astrocytoma.
format	article
author	Yasuhide Makino Yoshiki Arakawa Ema Yoshioka Tomoko Shofuda Takeshi Kawauchi Yukinori Terada Masahiro Tanji Daisuke Kanematsu Yohei Mineharu Susumu Miyamoto Yonehiro Kanemura
author_facet	Yasuhide Makino Yoshiki Arakawa Ema Yoshioka Tomoko Shofuda Takeshi Kawauchi Yukinori Terada Masahiro Tanji Daisuke Kanematsu Yohei Mineharu Susumu Miyamoto Yonehiro Kanemura
author_sort	Yasuhide Makino
title	Prognostic stratification for IDH-wild-type lower-grade astrocytoma by Sanger sequencing and copy-number alteration analysis with MLPA
title_short	Prognostic stratification for IDH-wild-type lower-grade astrocytoma by Sanger sequencing and copy-number alteration analysis with MLPA
title_full	Prognostic stratification for IDH-wild-type lower-grade astrocytoma by Sanger sequencing and copy-number alteration analysis with MLPA
title_fullStr	Prognostic stratification for IDH-wild-type lower-grade astrocytoma by Sanger sequencing and copy-number alteration analysis with MLPA
title_full_unstemmed	Prognostic stratification for IDH-wild-type lower-grade astrocytoma by Sanger sequencing and copy-number alteration analysis with MLPA
title_sort	prognostic stratification for idh-wild-type lower-grade astrocytoma by sanger sequencing and copy-number alteration analysis with mlpa
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/270c73917d924678a3734d63e82fb512
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Prognostic stratification for IDH-wild-type lower-grade astrocytoma by Sanger sequencing and copy-number alteration analysis with MLPA

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