المؤلفون: MOSQUERA ORGUEIRA, ADRIAN, Antelo Rodríguez, Beatriz, Alonso Vence, Natalia, Díaz Arias, José, Díaz Varela, Nicolás, Pérez Encinas, Manuel Mateo, Allegue Toscano, C., Goiricelaya Seco, E. M., Carracedo Álvarez, Ángel, Bello López, José Luis

مصطلحات موضوعية: Phosphoprotein Phosphatases, GTP-Binding Protein alpha Subunits, Survival Analysis, MAP Kinase Kinase Kinase 4, Humans, Association, Leukemia, Germ-Line Mutation, Genetic Predisposition to Disease, Prognosis, Gene Regulatory Networks, MAP cinasa cinasa cinasa 4, pronóstico, subunidades alfa de las proteínas de unión al GTP, humanos, análisis de supervivencia, fosfoproteína fosfatasas, leucemia, asociación, predisposición genética a la enfermedad, mutación de la línea germinal, redes génicas reguladoras, CHUS

الوصف: BACKGROUND: Chronic Lymphocytic Leukemia (CLL) is the most frequent lymphoproliferative disorder in western countries and is characterized by a remarkable clinical heterogeneity. During the last decade, multiple genomic studies have identified a myriad of somatic events driving CLL proliferation and aggressivity. Nevertheless, and despite the mounting evidence of inherited risk for CLL development, the existence of germline variants associated with clinical outcomes has not been addressed in depth. METHODS: Exome sequencing data from control leukocytes of CLL patients involved in the International Cancer Genome Consortium (ICGC) was used for genotyping. Cox regression was used to detect variants associated with clinical outcomes. Gene and pathways level associations were also calculated. RESULTS: Single nucleotide polymorphisms in PPP4R2 and MAP3K4 were associated with earlier treatment need. A gene-level analysis evidenced a significant association of RIPK3 with both treatment need and survival. Furthermore, germline variability in pathways such as apoptosis, cell-cycle, pentose phosphate, GNalpha13 and Nitric oxide was associated with overall survival. CONCLUSION: Our results support the existence of inherited conditionants of CLL evolution and points towards genes and pathways that may results useful as biomarkers of disease outcome. More research is needed to validate these findings.

العلاقة: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542042/pdf/12885_2019_Article_5628.pdfTest; https://www.ncbi.nlm.nih.gov/pubmed/31142279Test; http://hdl.handle.net/20.500.11940/15774Test; 31789

الإتاحة: https://doi.org/20.500.11940/15774Test
https://doi.org/10.1186/s12885-019-5628-yTest
https://hdl.handle.net/20.500.11940/15774Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542042/pdf/12885_2019_Article_5628.pdfTest
https://www.ncbi.nlm.nih.gov/pubmed/31142279Test

المؤلفون: Schepers, E., Lousberg, R., Guloksuz, S., Pries, L. K., Delespaul, P., Kenis, G., Luykx, J. J., Lin, B. D., Richards, A. L., Akdede, B., Binbay, T., Altınyazar, V., Yalınçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Şahin Cankurtaran, E., Ulusoy Kaymak, S., Mihaljevic, M. M., Andric Petrovic, S., Mirjanic, T., Bernardo, M., Cabrera, B., Bobes, J., Saiz, P. A., García-Portilla, M. P., Sanjuan, J., Aguilar, E. J., Luis Santos, J., Jiménez-López, E., ARROJO ROMERO, MANUEL, Carracedo Álvarez, Ángel, López, G., González-Peñas, J., Parellada, M., Maric, N. P., Atbaşoğlu, C., Ucok, A., Alptekin, K., Can Saka, M., Arango, C., Rutten, B. P. F., van Os, J.

مصطلحات موضوعية: FPGMX, CHUS, IDIS

الوصف: Introduction: White noise speech illusions index liability for psychotic disorder in case-control comparisons. In the current study, we examined i) the rate of white noise speech illusions in siblings of patients with psychotic disorder and ii) to what degree this rate would be contingent on exposure to known environmental risk factors (childhood adversity and recent life events) and level of known endophenotypic dimensions of psychotic disorder [psychotic experiences assessed with the Community Assessment of Psychic Experiences (CAPE) scale and cognitive ability]. Methods: The white noise task was used as an experimental paradigm to elicit and measure speech illusions in 1,014 patients with psychotic disorders, 1,157 siblings, and 1,507 healthy participants. We examined associations between speech illusions and increasing familial risk (control -> sibling -> patient), modeled as both a linear and a categorical effect, and associations between speech illusions and level of childhood adversities and life events as well as with CAPE scores and cognitive ability scores. Results: While a positive association was found between white noise speech illusions across hypothesized increasing levels of familial risk (controls -> siblings -> patients) [odds ratio (OR) linear 1.11, 95% confidence interval (CI) 1.02-1.21, p = 0.019], there was no evidence for a categorical association with sibling status (OR 0.93, 95% CI 0.79-1.09, p = 0.360). The association between speech illusions and linear familial risk was greater if scores on the CAPE positive scale were higher (p interaction = 0.003; ORlow CAPE positive scale 0.96, 95% CI 0.85-1.07; ORhigh CAPE positive scale 1.26, 95% CI 1.09-1.46); cognitive ability was lower (p interaction < 0.001; ORhigh cognitive ability 0.94, 95% CI 0.84-1.05; ORlow cognitive ability 1.43, 95% CI 1.23-1.68); and exposure to childhood adversity was higher (p interaction < 0.001; ORlow adversity 0.92, 95% CI 0.82-1.04; ORhigh adversity 1.31, 95% CI 1.13-1.52). A similar, although ...

العلاقة: https://www.ncbi.nlm.nih.gov/pubmed/31607966Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774265/pdf/fpsyt-10-00676.pdfTest; http://hdl.handle.net/20.500.11940/15546Test; 30988

الإتاحة: https://doi.org/20.500.11940/15546Test
https://doi.org/10.3389/fpsyt.2019.00676Test
https://hdl.handle.net/20.500.11940/15546Test
https://www.ncbi.nlm.nih.gov/pubmed/31607966Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774265/pdf/fpsyt-10-00676.pdfTest

المؤلفون: Fernández Rozadilla, Ceres, Alvarez-Barona, M., Schamschula, E., Bodo, S., López Novo, Anael, Dacal Rivas, Andrés, Calviño Costas, Consuelo, Lancho Seco, Ángel, Amigo Lechuga, Jorge, Bello, X., Cameselle Teijeiro, Jose Manuel, Carracedo Álvarez, Ángel, Colas, C., Muleris, M., Wimmer, K., Ruiz Ponte, Clara

مصطلحات موضوعية: FPGMX, CHUS, HULA

الوصف: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by heterozygous mutations in the mismatch repair (MMR) genes. Biallelic mutations in these genes lead however, to constitutive mismatch repair deficiency (CMMRD). In this study, we follow the diagnostic journey of a 12-year old patient with CRC, with a clinical phenotype overlapping CMMRD. We perform molecular and functional assays to discard a CMMRD diagnosis then identify by exome sequencing and validation in a cohort of 134 LS patients, a candidate variant in the MLH1 UTR region in homozygosis. We propose that this variant, together with other candidates, could be responsible for age-of-onset modulation. Our data support the idea that low-risk modifier alleles may influence early development of cancer in LS leading to a LS-to-CMMRD phenotypic continuum. Therefore, it is essential that larger efforts are directed to the identification and study of these genetic modifiers, in order to provide optimal cancer prevention strategies to these patients.

العلاقة: https://res.mdpi.com/d_attachment/cancers/cancers-11-01081/article_deploy/cancers-11-01081-v2.pdfTest; https://www.ncbi.nlm.nih.gov/pubmed/31366136Test; http://hdl.handle.net/20.500.11940/15435Test; 30725

الإتاحة: https://doi.org/20.500.11940/15435Test
https://doi.org/10.3390/cancers11081081Test
https://hdl.handle.net/20.500.11940/15435Test
https://www.ncbi.nlm.nih.gov/pubmed/31366136Test

المؤلفون: Ferrer, A., Labad, J., Salvat-Pujol, N., Barrachina, M., Costas Costas, Javier, Urretavizcaya, M., de Arriba-Arnau, A., Crespo, J. M., Soriano-Mas, C., Carracedo Álvarez, Ángel, Menchón, J. M., Soria, V.

مصطلحات موضوعية: Middle Aged, Humans, Depressive Disorder, Case-Control Studies, Neuropsychological Tests, estudios de casos y controles, pruebas neuropsicológicas, mediana edad, humanos, trastorno depresivo, FPGMX, IDIS, CHUS

الوصف: Brain-derived neurotrophic factor (BDNF) gene regulation has been linked to the pathophysiology of major depressive disorder (MDD). MDD patients show cognitive deficits, and altered BDNF regulation has a relevant role in neurocognitive functions. Our goal was to explore the association between BDNF genetic and epigenetic variations with neurocognitive performance in a group of MDD patients and healthy controls considering possible modulating factors. The sample included 134 subjects, 64 MDD patients, and 70 healthy controls. Clinical data, childhood maltreatment, and neurocognitive performance were assessed in all participants. Eleven single nucleotide polymorphisms (SNPs) and two promoter regions in the BDNF gene were selected for genotype and methylation analysis. The role of interactions between BDNF genetic and epigenetic variations with MDD diagnosis, sex, and Childhood Trauma Questionnaire (CTQ) scores was also explored. We observed significant associations between neurocognitive performance and two BDNF SNPs (rs908867 and rs925946), an effect that was significantly mediated by methylation values at specific promoter I sites. We identified significant associations between neurocognitive results and methylation status as well as its interactions with MDD diagnosis, sex, and CTQ scores. Our results support the hypothesis that BDNF gene SNPs and methylation status, as well as their interactions with modulating factors, can influence cognition. Further studies are required to confirm the effect of BDNF variations and cognitive function in larger samples.

العلاقة: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803763/pdf/41398_2019_Article_601.pdfTest; https://www.ncbi.nlm.nih.gov/pubmed/31636250Test; http://hdl.handle.net/20.500.11940/15440Test; 30738

الإتاحة: https://doi.org/20.500.11940/15440Test
https://doi.org/10.1038/s41398-019-0601-8Test
https://hdl.handle.net/20.500.11940/15440Test
https://www.ncbi.nlm.nih.gov/pubmed/31636250Test