000			02489na a2200325 4500
999			_c7044 _d7044
003			PC7044
005			20190617134519.0
008			130622s2013 xxx||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_aHernández Laín, Aurelio _9624 _e Anatomía Patológica
245	0	0	_aIntegrated analysis of mismatch repair system in malignant astrocytomas. _h[artículo]
260			_bPloS one, _c2013
300			_a8(9):e76401.
500			_aFormato Vancouver: Rodríguez-Hernández I, García JL, Santos-Briz A, Hernández-Laín A, González-Valero JM, Gómez-Moreta JA et al. Integrated analysis of mismatch repair system in malignant astrocytomas. PLoS One. 2013 Sep 20;8(9):e76401.
501			_aPMID: 24073290
504			_aContiene 52 referencias
520			_aMalignant 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.
710			_9330 _aServicio de Anatomía Patológica
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779191/pdf/pone.0076401.pdf _yAcceso libre
942			_n0 _2ddc _cART