Integrated analysis of mismatch repair system in malignant astrocytomas.

Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR) system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize...

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Autores principales:	Irene Rodríguez-Hernández, Juan Luis Garcia, Angel Santos-Briz, Aurelio Hernández-Laín, Jose María González-Valero, Juan Antonio Gómez-Moreta, Oscar Toldos-González, Juan Jesús Cruz, Javier Martin-Vallejo, Rogelio González-Sarmiento
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/22bad0908c5d4b80bab0b38397be9578
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spelling	oai:doaj.org-article:22bad0908c5d4b80bab0b38397be95782021-11-18T08:54:15ZIntegrated analysis of mismatch repair system in malignant astrocytomas.1932-620310.1371/journal.pone.0076401https://doaj.org/article/22bad0908c5d4b80bab0b38397be95782013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24073290/?tool=EBIhttps://doaj.org/toc/1932-6203Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR) system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI) and MMR gene mutations in a set of 96 low- and high-grade astrocytomas. Forty-one astrocytomas failed to express at least one MMR protein. Loss of MSH2 expression was more frequent in low-grade astrocytomas. Loss of MLH1 expression was associated with MLH1 promoter hypermethylation and MLH1-93G>A promoter polymorphism. However, MSI was not related with MMR protein expression and only 5% of tumors were MSI-High. Furthermore, the incidence of tumors carrying germline mutations in MMR genes was low and only one glioblastoma was associated with Lynch syndrome. Interestingly, survival analysis identified that tumors lacking MSH6 expression presented longer overall survival in high-grade astrocytoma patients treated only with radiotherapy while MSH6 expression did not modify the prognosis of those patients treated with both radiotherapy and chemotherapy. Our findings suggest that MMR system alterations are a frequent event in malignant astrocytomas and might help to define a subgroup of patients with different outcome.Irene Rodríguez-HernándezJuan Luis GarciaAngel Santos-BrizAurelio Hernández-LaínJose María González-ValeroJuan Antonio Gómez-MoretaOscar Toldos-GonzálezJuan Jesús CruzJavier Martin-VallejoRogelio González-SarmientoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e76401 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Irene Rodríguez-Hernández Juan Luis Garcia Angel Santos-Briz Aurelio Hernández-Laín Jose María González-Valero Juan Antonio Gómez-Moreta Oscar Toldos-González Juan Jesús Cruz Javier Martin-Vallejo Rogelio González-Sarmiento Integrated analysis of mismatch repair system in malignant astrocytomas.
description	Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR) system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI) and MMR gene mutations in a set of 96 low- and high-grade astrocytomas. Forty-one astrocytomas failed to express at least one MMR protein. Loss of MSH2 expression was more frequent in low-grade astrocytomas. Loss of MLH1 expression was associated with MLH1 promoter hypermethylation and MLH1-93G>A promoter polymorphism. However, MSI was not related with MMR protein expression and only 5% of tumors were MSI-High. Furthermore, the incidence of tumors carrying germline mutations in MMR genes was low and only one glioblastoma was associated with Lynch syndrome. Interestingly, survival analysis identified that tumors lacking MSH6 expression presented longer overall survival in high-grade astrocytoma patients treated only with radiotherapy while MSH6 expression did not modify the prognosis of those patients treated with both radiotherapy and chemotherapy. Our findings suggest that MMR system alterations are a frequent event in malignant astrocytomas and might help to define a subgroup of patients with different outcome.
format	article
author	Irene Rodríguez-Hernández Juan Luis Garcia Angel Santos-Briz Aurelio Hernández-Laín Jose María González-Valero Juan Antonio Gómez-Moreta Oscar Toldos-González Juan Jesús Cruz Javier Martin-Vallejo Rogelio González-Sarmiento
author_facet	Irene Rodríguez-Hernández Juan Luis Garcia Angel Santos-Briz Aurelio Hernández-Laín Jose María González-Valero Juan Antonio Gómez-Moreta Oscar Toldos-González Juan Jesús Cruz Javier Martin-Vallejo Rogelio González-Sarmiento
author_sort	Irene Rodríguez-Hernández
title	Integrated analysis of mismatch repair system in malignant astrocytomas.
title_short	Integrated analysis of mismatch repair system in malignant astrocytomas.
title_full	Integrated analysis of mismatch repair system in malignant astrocytomas.
title_fullStr	Integrated analysis of mismatch repair system in malignant astrocytomas.
title_full_unstemmed	Integrated analysis of mismatch repair system in malignant astrocytomas.
title_sort	integrated analysis of mismatch repair system in malignant astrocytomas.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/22bad0908c5d4b80bab0b38397be9578
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Integrated analysis of mismatch repair system in malignant astrocytomas.

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