DBIOQ. Bioquímica, Microbiología, Biología Celular y Genética
http://riull.ull.es/xmlui/handle/915/4109
Documentos de investigación (artículos, libros, capítulos de libros, ponencias...) publicados por investigadores del Departamento de Bioquímica, Microbiología, Biología Celular y Genéica2024-03-28T08:26:42ZMatched Paired Primary and Recurrent meningiomasPoints to cell death program contributions to Genomic and epigenomic instability along
tumor progression
http://riull.ull.es/xmlui/handle/915/36191
Matched Paired Primary and Recurrent meningiomasPoints to cell death program contributions to Genomic and epigenomic instability along
tumor progression
San-Miguel, Teresa; Megías Vericat, Javier; Monleón, Daniel; Navarro Cerveró, Lara; Muñoz-Hidalgo, Lisandra; Montoliu Félix, Carmina; Meri-Abad, Marina; Roldán, Pedro; Cerdá-Nicolás, Miguel; López-Ginés, Concha
Meningioma (MN) is an important cause of disability, and predictive tools for estimating the risk of recurrence are still scarce. The need for objective and cost-effective techniques addressed to this purpose is well known. In this study, we present methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a friendly method for deepening the understanding of the mechanisms underlying meningioma progression. A large follow-up allowed us to obtain 50 samples, which included the primary tumor of 20 patients in which half of them are suffering one recurrence and the other half are suffering more than one. We histologically characterized the samples and performed MS-MLPA assays validated by FISH to assess their copy number alterations (CNA) and epigenetic status. Interestingly, we determined the increase in tumor instability with higher values of CNA during the progression accompanied by an increase in epigenetic damage. We also found a loss of HIC1 and the hypermethylation of CDKN2B and PTEN as independent prognostic markers. Comparison between grade 1 and higher primary MN’s self-evolution pointed to a central role of GSTP1 in the first stages of the disease. Finally, a high rate of alterations in genes that are related to apoptosis and autophagy, such as DAPK1, PARK2, BCL2, FHIT, or VHL, underlines an important influence on cell-death programs through different pathways.
2022-01-01T00:00:00ZCorrelation between EGFR amplification and the expression of microRNA-200c in primary Glioblastoma multiforme
http://riull.ull.es/xmlui/handle/915/36190
Correlation between EGFR amplification and the expression of microRNA-200c in primary Glioblastoma multiforme
Serna, Eva; López Ginés, Concha; Monleón, Daniel; Muñoz-Hidalgo, Lisandra; Callaghan, Robert C.; Gil-Benso, Rosario; Martinetto, Horacio; Gregori-Romero, María Aurelia; González-Darder, José Manuel; Cerdá-Nicolás, Miguel J.
Extensive infiltration of the surrounding healthy brain tissue is a critical feature in glioblastoma. Several miRNAs have been related to gliomagenesis, some of them related with the EGFR pathway. We have evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns, studied by fluorescence in situ hybridization in tissue microarrays, of 30 cases of primary glioblastoma multiforme, whose clinicopathological and immunohistochemical features have also been analyzed. MicroRNA-200c showed a very significant difference between tumors having or not EGFR amplification. This microRNA plays an important role in epithelial-mesenchymal transition, but its implication in the behavior of glioblastoma is largely unknown. With respect to EGFR status our cases were categorized into three groups: high level EGFR amplification, low level EGFR amplification, and no EGFR amplification. Our results showed that microRNA-200c and E-cadherin expression are down-regulated, while ZEB1 is up-regulated, when tumors showed a high level of EGFR amplification. Conversely, ZEB1 mRNA expression levels were significantly lower in the group of tumors without EGFR amplification. Tumors with a low level of EGFR amplification showed ZEB1 expression levels comparable to those detected in the group with a high level of amplification. In this study we provide what is to our knowledge the first report of association between microRNA-200c and EGFR amplification in glioblastomas.
2014-01-01T00:00:00ZIdentification of a novel BRCA1 alteration in recurrent melanocytoma resulting in an increased proliferation
http://riull.ull.es/xmlui/handle/915/36189
Identification of a novel BRCA1 alteration in recurrent melanocytoma resulting in an increased proliferation
San-Miguel, Teresa; Navarro Cerveró, Lara; Sánchez-Sendra, Beatriz; Megías Vericat, Javier; Muñoz-Hidalgo, Lisandra; Santonja-López, Nuria; López-Ginés, Concha; Cerdá-Nicolás, Miguel J.
Primary meningeal melanocytomas are rare tumors of the central nervous system. Although they are considered benign neoplasms, some reports describe recurrent rates up to 45%. Little is known about their genetic and epigenetic landscape because of their infrequency. Even less has been described about markers with prognostic value. Here we describe a patient who developed a primary meningeal melanocytoma, suffered 3 recurrences in a period of 6 years and died of the tumor. The genetic and epigenetic changes explored confirmed GNAQ mutation as an initiating event. We found an epigenetic alteration of GSTP1, a feature that has recently been described in meningiomas, from the beginning of the disease. In addition, there was loss of heterozygosity in BRCA1 beginning in the second recurrence that was linked to an increase in the proliferation index; this suggested a progression pathway similar to the one described in uveal melanomas. These findings underscore the necessity of further research focused on these tumors.
2020-01-01T00:00:00ZMolecular progression in unusual recurrent non-pediatric intracranial clear cell meningioma.
http://riull.ull.es/xmlui/handle/915/36188
Molecular progression in unusual recurrent non-pediatric intracranial clear cell meningioma.
Domingo-Arrué, B.; Gil-Benso, Rosario; Megías Vericat, Javier; Navarro Cerveró, Lara; San-Miguel, Teresa; Muñoz-Hidalgo, Lisandra; López Ginés, Concha; Cerdá-Nicolás, Miguel J.
We report a case of a recurrent clear cell meningioma (ccm) in the frontal lobe of the brain of a 67-year-old man. The patient developed three recurrences: at 3, 10, and 12 years after his initial surgery. Histopathology observations revealed a grade 2 ccm with positivity for vimentin and epithelial membrane antigen. Expression of E-cadherin was positive only in the primary tumour and in the first available recurrence. Fluorescence in situ hybridization analyses demonstrated 1p and 14q deletions within the last recurrence. Multiplex ligation-dependent probe amplification studies revealed a heterozygous partial NF2 gene deletion, which progressed to total loss in the last recurrence. The last recurrence showed homozygous deletions in CDKN2A and CDKN2B. The RASSF1 gene was hypermethylated during tumour evolution. In this report, we show the genetic alterations of a primary ccm and its recurrences to elucidate their relationships with the changes involved in the progression of this rare neoplasm.
2017-01-01T00:00:00Z