Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns

Abstract The great majority of sporadic vestibular schwannomas (VSs) are due to the inactivation of the NF2 gene. In this study, we found age-dependent differences in the clinical parameters of sporadic VSs. Young patients were characterized by progressive tumour behaviours, including earlier onset...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hongsai Chen, Lu Xue, Hantao Wang, Zhaoyan Wang, Hao Wu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f2500654f84a4562bd5facdeb9301b19
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f2500654f84a4562bd5facdeb9301b19
record_format	dspace
spelling	oai:doaj.org-article:f2500654f84a4562bd5facdeb9301b192021-12-02T11:41:19ZDifferential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns10.1038/s41598-017-05769-02045-2322https://doaj.org/article/f2500654f84a4562bd5facdeb9301b192017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05769-0https://doaj.org/toc/2045-2322Abstract The great majority of sporadic vestibular schwannomas (VSs) are due to the inactivation of the NF2 gene. In this study, we found age-dependent differences in the clinical parameters of sporadic VSs. Young patients were characterized by progressive tumour behaviours, including earlier onset of initial symptoms, shorter symptom duration and larger tumour size. An increased rate of “two-hits” of both NF2 alleles, usually by mutation and allelic loss, was observed in young cases compared to older, and this correlated with the loss of protein and mRNA expression. In contrast, the tumours with a single mutation (referred to as ‘one-hit’) exhibited obvious expression levels. Moreover, a mixture of merlin-expressing tumour cells and non-expressing tumour cells was observed in ‘one-hit’ schwannomas, suggesting that a subset of ‘one-hit’ tumour cells was present in these tumours. To mimic the growth promoting effects by the second hit, we performed lentivirus-mediated NF2 knockdown in the ‘one-hit’ schwannoma cultures. Following the loss of NF2 expression, schwannoma cultures demonstrated increased proliferation rates. Above all, we have identified a correlation between the NF2 status and the growth patterns of sporadic VSs. The treatment decision-making, microsurgery or “wait and scan” strategy, should be carried out according to the tumour’s genetic background.Hongsai ChenLu XueHantao WangZhaoyan WangHao WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hongsai Chen Lu Xue Hantao Wang Zhaoyan Wang Hao Wu Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns
description	Abstract The great majority of sporadic vestibular schwannomas (VSs) are due to the inactivation of the NF2 gene. In this study, we found age-dependent differences in the clinical parameters of sporadic VSs. Young patients were characterized by progressive tumour behaviours, including earlier onset of initial symptoms, shorter symptom duration and larger tumour size. An increased rate of “two-hits” of both NF2 alleles, usually by mutation and allelic loss, was observed in young cases compared to older, and this correlated with the loss of protein and mRNA expression. In contrast, the tumours with a single mutation (referred to as ‘one-hit’) exhibited obvious expression levels. Moreover, a mixture of merlin-expressing tumour cells and non-expressing tumour cells was observed in ‘one-hit’ schwannomas, suggesting that a subset of ‘one-hit’ tumour cells was present in these tumours. To mimic the growth promoting effects by the second hit, we performed lentivirus-mediated NF2 knockdown in the ‘one-hit’ schwannoma cultures. Following the loss of NF2 expression, schwannoma cultures demonstrated increased proliferation rates. Above all, we have identified a correlation between the NF2 status and the growth patterns of sporadic VSs. The treatment decision-making, microsurgery or “wait and scan” strategy, should be carried out according to the tumour’s genetic background.
format	article
author	Hongsai Chen Lu Xue Hantao Wang Zhaoyan Wang Hao Wu
author_facet	Hongsai Chen Lu Xue Hantao Wang Zhaoyan Wang Hao Wu
author_sort	Hongsai Chen
title	Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns
title_short	Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns
title_full	Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns
title_fullStr	Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns
title_full_unstemmed	Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns
title_sort	differential nf2 gene status in sporadic vestibular schwannomas and its prognostic impact on tumour growth patterns
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f2500654f84a4562bd5facdeb9301b19
work_keys_str_mv	AT hongsaichen differentialnf2genestatusinsporadicvestibularschwannomasanditsprognosticimpactontumourgrowthpatterns AT luxue differentialnf2genestatusinsporadicvestibularschwannomasanditsprognosticimpactontumourgrowthpatterns AT hantaowang differentialnf2genestatusinsporadicvestibularschwannomasanditsprognosticimpactontumourgrowthpatterns AT zhaoyanwang differentialnf2genestatusinsporadicvestibularschwannomasanditsprognosticimpactontumourgrowthpatterns AT haowu differentialnf2genestatusinsporadicvestibularschwannomasanditsprognosticimpactontumourgrowthpatterns
_version_	1718395437164003328

Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns

Ejemplares similares