19 results on '"Rosas-Alonso R"'
Search Results
2. Glioma Patient Management: Utilizing MGMT Methylation in Extracellular Vesicle-Based Liquid Biopsy
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De Caceres, I. Ibanez, Rosas-Alonso, R., Pernia, O., Burdiel, M., Rodriguez-Antolin, C., Moreno, R., Esteban-Rodriguez, I., Martinez, V., and de Castro, J.
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- 2023
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3. EP16.02-014 A Comparative Analysis of Gene Alteration Detected With NGS in Tumor Tissue and Peripheral Blood in Lung Cancer
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Ozaez, I., primary, Hernández, I., additional, Cruz-Castellanos, P., additional, Gutiérrez-Sainz, L., additional, Rosas-Alonso, R., additional, Castillo, R., additional, Higuera, O., additional, Losantos, I., additional, Rodríguez-Antolín, C., additional, Ibanez de Caceres, I., additional, Rodríguez, I. Esteban, additional, and de Castro Carpeño, J., additional
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- 2022
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4. EP08.02-088 Mutational Status of KRAS, STK11 and CDKN2A Genes as Predictors of Response to Antiangiogenic Agents in Non-small Cell Lung Cancer Patients
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Cruz Castellanos, P., primary, Rosas Alonso, R., additional, Ozaez, I., additional, Hernández, I., additional, Losantos, I., additional, Gutiérrez Sainz, L., additional, Higuera Gómez, O., additional, Rodríguez Antolín, C., additional, Esteban Rodríguez, I., additional, Ibáñez de Cáceres, I., additional, and De Castro Carpeño, J., additional
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- 2022
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5. EP.12C.04 Location of Metastases and Prognosis of Patients with Metastatic KRAS-Mutant Non-Small Cell Lung Cancer
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Gutiérrez Sainz, L., Ozáez, I., Higuera Gómez, O., Villamayor, J., Esteban Rodríguez, I., Regojo Zapata, R.M., Peláez García, A., Heredia Soto, V., Mendiola, M., Rosas Alonso, R., Rodríguez Antolín, C., Ibáñez de Cáceres, I., and de Castro Carpeño, J.
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- 2024
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6. Next-generation sequencing panel verification to detect low frequency single nucleotide and copy number variants from mixing cell line studies
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Rosas-Alonso, R., primary, Rodriguez-Antolin, C., additional, Esteban Rodriguez, I., additional, Cruz Castellanos, P., additional, de Castro Carpeño, J., additional, and Ibanez de Caceres, I., additional
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- 2019
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7. 1419P - Next-generation sequencing panel verification to detect low frequency single nucleotide and copy number variants from mixing cell line studies
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Rosas-Alonso, R., Rodriguez-Antolin, C., Esteban Rodriguez, I., Cruz Castellanos, P., de Castro Carpeño, J., and Ibanez de Caceres, I.
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- 2019
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8. Evaluation of the clinical use of MGMT methylation in extracellular vesicle-based liquid biopsy as a tool for glioblastoma patient management.
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Rosas-Alonso R, Colmenarejo-Fernández J, Pernía O, Burdiel M, Rodríguez-Antolín C, Losantos-García I, Rubio T, Moreno-Velasco R, Esteban-Rodríguez I, Martínez-Marín V, Yubero P, Costa-Fraga N, Díaz-Lagares A, López-López R, Díaz-Martin E, García JF, Sánchez CV, Gandía-González ML, Moreno-Bueno G, de Castro J, and de Cáceres II
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- Humans, Liquid Biopsy methods, Male, Female, Middle Aged, Aged, Adult, Prognosis, Glioblastoma genetics, Glioblastoma pathology, Glioblastoma diagnosis, Extracellular Vesicles metabolism, Extracellular Vesicles genetics, DNA Modification Methylases genetics, DNA Modification Methylases metabolism, DNA Repair Enzymes genetics, DNA Repair Enzymes metabolism, DNA Methylation, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Brain Neoplasms genetics, Brain Neoplasms pathology, Brain Neoplasms diagnosis
- Abstract
Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings., (© 2024. The Author(s).)
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- 2024
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9. MiR-151a: a robust endogenous control for normalizing small extracellular vesicle cargo in human cancer.
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Burdiel M, Jiménez J, Rodríguez-Antolín C, García-Guede Á, Pernía O, Sastre-Perona A, Rosas-Alonso R, Colmenarejo J, Rodríguez-Jiménez C, Diestro MD, Martínez-Marín V, Higueras O, Cruz P, Losantos-García I, Peinado H, Vera O, de Castro J, and Ibáñez de Cáceres I
- Abstract
Small extracellular vesicles (sEVs) in the blood of cancer patients contain higher amounts of tumor markers than those identified as free-circulating. miRNAs have significant biomedical relevance due to their high stability and feasible detection. However, there is no reliable endogenous control available to measure sEVs-miRNA content, impairing the acquisition of standardized consistent measurements in cancer liquid biopsy. In this study, we identified three miRNAs from a panel of nine potential normalizers that emerged from a comprehensive analysis comparing the sEV-miRNA profile of six lung and ovarian human cancer cell lines in the absence of or under different conditions. Their relevance as normalizers was tested in 26 additional human cancer cell lines from nine different tumor types undergoing chemotherapy or radiotherapy treatment. The validation cohorts were comprised of 242 prospective plasma and ascitic fluid samples from three different human tumor types. Variability and normalization properties were tested in comparison to miR-16, the most used control to normalize free-circulating miRNAs in plasma. Our results indicate that miR-151a is consistently represented in small extracellular vesicles with minimal variability compared to miR-16, providing a novel normalizer to measure small extracellular vesicle miRNA content that will benefit liquid biopsy in cancer patients., (© 2023. Yumed Inc. and BioMed Central Ltd., part of Springer Nature.)
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- 2023
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10. Advancing pharmacogenetic testing in a tertiary hospital: a retrospective analysis after 10 years of activity.
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Stewart S, Dodero-Anillo JM, Guijarro-Eguinoa J, Arias P, Gómez López De Las Huertas A, Seco-Meseguer E, García-García I, Ramírez García E, Rodríguez-Antolín C, Carcas AJ, Rodriguez-Novoa S, Rosas-Alonso R, and Borobia AM
- Abstract
The field of pharmacogenetics (PGx) holds great promise in advancing personalized medicine by adapting treatments based on individual genetic profiles. Despite its benefits, there are still economic, ethical and institutional barriers that hinder its implementation in our healthcare environment. A retrospective analysis approach of anonymized data sourced from electronic health records was performed, encompassing a diverse patient population and evaluating key parameters such as prescribing patterns and test results, to assess the impact of pharmacogenetic testing. A head-to-head comparison with previously published activity results within the same pharmacogenetic laboratory was also conducted to contrast the progress made after 10 years. The analysis revealed significant utilization of pharmacogenetic testing in daily clinical practice, with 1,145 pharmacogenetic tests performed over a 1-year period and showing a 35% growth rate increase over time. Of the 17 different medical departments that sought PGx tests, the Oncology department accounted for the highest number, representing 58.47% of all genotyped patients. A total of 1,000 PGx tests were requested for individuals susceptible to receive a dose modification based on genotype, and 76 individuals received a genotype-guided dose adjustment. This study presents a comprehensive descriptive analysis of real-world data obtained from a public tertiary hospital laboratory specialized in pharmacogenetic testing, and presents data that strongly endorse the integration of pharmacogenetic testing into everyday clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Stewart, Dodero-Anillo, Guijarro-Eguinoa, Arias, Gómez López De Las Huertas, Seco-Meseguer, García-García, Ramírez García, Rodríguez-Antolín, Carcas, Rodriguez-Novoa, Rosas-Alonso and Borobia.)
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- 2023
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11. miR-124 as a Liquid Biopsy Prognostic Biomarker in Small Extracellular Vesicles from NSCLC Patients.
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Sanchez-Cabrero D, Garcia-Guede Á, Burdiel M, Pernía O, Colmenarejo-Fernandez J, Gutierrez L, Higuera O, Rodriguez IE, Rosas-Alonso R, Rodriguez-Antolín C, Losantos-García I, Vera O, De Castro-Carpeño J, and Ibanez de Caceres I
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- Humans, Prognosis, Prospective Studies, Biomarkers, Tumor metabolism, Neoplasm Recurrence, Local metabolism, Liquid Biopsy, Proteoglycans metabolism, alpha Karyopherins metabolism, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms diagnosis, Lung Neoplasms genetics, Lung Neoplasms pathology, MicroRNAs metabolism, Exosomes metabolism
- Abstract
Despite advances in non-small cell lung cancer (NSCLC) research, this is still the most common cancer type that has been diagnosed up to date. microRNAs have emerged as useful clinical biomarkers in both tissue and liquid biopsy. However, there are no reliable predictive biomarkers for clinical use. We evaluated the preclinical use of seven candidate miRNAs previously identified by our group. We collected a total of 120 prospective samples from 88 NSCLC patients. miRNA levels were analyzed via qRT-PCR from tissue and blood samples. miR-124 gene target prediction was performed using RNA sequencing data from our group and interrogating data from 2952 NSCLC patients from two public databases. We found higher levels of all seven miRNAs in tissue compared to plasma samples, except for miR-124. Our findings indicate that levels of miR-124, both free-circulating and within exosomes, are increased throughout the progression of the disease, suggesting its potential as a marker of disease progression in both advanced and early stages. Our bioinformatics approach identified KPNA4 and SPOCK1 as potential miR-124 targets in NSCLC. miR-124 levels can be used to identify early-stage NSCLC patients at higher risk of relapse.
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- 2023
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12. Identifying biomarkers of treatment response to ciclosporin in atopic dermatitis through multiomic predictive modelling: DERMATOMICS study protocol.
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Marín-Candón A, García-García I, Arias P, Carcas AJ, Díaz-García L, Feltes Ochoa R, Hernández Cano N, Herranz Pinto P, Jiménez González M, López-Granados E, Martínez-Feito A, Mayor-Ibarguren A, Rosas-Alonso R, Seco-Meseguer E, and Borobia AM
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- Humans, Biomarkers, Multiomics, Retrospective Studies, Clinical Trials, Phase IV as Topic, Cyclosporine therapeutic use, Dermatitis, Atopic drug therapy
- Abstract
Introduction: There is a need to optimise the management of atopic dermatitis (AD), improving the efficacy of treatments and reducing the toxicity associated with them. Although the efficacy of ciclosporine (CsA) in the treatment of AD has been thoroughly documented in the literature, the optimal dose has not been yet established. The use of multiomic predictive models of treatment response could optimise CsA therapy in AD., Methods and Analysis: The study is a low-intervention phase 4 trial to optimise the treatment of patients with moderate-severe AD requiring systemic treatment. The primary objectives are to identify biomarkers that could allow for the selection of responders and non-responders to first-line treatment with CsA and to develop a response prediction model to optimise the CsA dose and treatment regimen in responding patients based on these biomarkers. The study is divided into two cohorts: the first comprised of patients starting treatment with CsA (cohort 1), and the second, of patients already receiving or who have received CsA therapy (cohort 2)., Ethics and Dissemination: The study activities began following authorisation by the Spanish Regulatory Agency (AEMPS) and the Clinical Research Ethics Committee of La Paz University Hospital approval. Trial results will be submitted for publication in an open access peer-reviewed medical speciality-specific publication.Trial registration of this study can be located at the EU Clinical Trials Register, available from https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en. Our clinical trial was registered in the website before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according the WHO. Once our trial was included in a primary and official registry, in order to extend the accessibility to our research, we also registered it retrospectively in clinicaltrials.gov; however, this is not mandatory as per our regulation., Trial Registration Number: NCT05692843., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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13. Prognostic Impact of Dihydropyrimidine Dehydrogenase Germline Variants in Unresectable Non-Small Cell Lung Cancer Patients Treated with Platin-Based Chemotherapy.
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Guijarro-Eguinoa J, Arjona-Hernandez S, Stewart S, Pernia O, Arias P, Losantos-García I, Rubio T, Burdiel M, Rodriguez-Antolin C, Cruz-Castellanos P, Higuera O, Borobia AM, Rodriguez-Novoa S, de Castro-Carpeño J, Ibanez de Caceres I, and Rosas-Alonso R
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- Humans, Dihydrouracil Dehydrogenase (NADP) genetics, Fluorouracil therapeutic use, Prognosis, Germ Cells, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms chemically induced
- Abstract
Platin-based chemotherapy is the standard treatment for patients with non-small cell lung cancer (NSCLC). However, resistance to this therapy is a major obstacle in successful treatment. In this study, we aimed to investigate the impact of several pharmacogenetic variants in patients with unresectable NSCLC treated with platin-based chemotherapy. Our results showed that DPYD variant carriers had significantly shorter progression-free survival and overall survival compared to DPYD wild-type patients, whereas DPD deficiency was not associated with a higher incidence of high-grade toxicity. For the first time, our study provides evidence that DPYD gene variants are associated with resistance to platin-based chemotherapy in NSCLC patients. Although further studies are needed to confirm these findings and explore the underlying mechanisms of this association, our results suggest that genetic testing of DPYD variants may be useful for identifying patients at a higher risk of platin-based chemotherapy resistance and might be helpful in guiding future personalized treatment strategies in NSCLC patients.
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- 2023
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14. Analytical validation of a laboratory-development multigene pharmacogenetic assay.
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Rosas-Alonso R, Queiruga J, Arias P, Del Monte Á, Yuste F, Rodríguez-Antolín C, Losantos-Garcia I, Borobia AM, and Rodríguez-Nóvoa S
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- Humans, Laboratories, Pharmacogenomic Testing, Reproducibility of Results, Laboratories, Clinical, Pharmacogenetics
- Abstract
Objective: The implementation of pharmacogenetics (PGx) in clinical practice is an essential tool for personalized medicine. However, clinical laboratories must validate their procedures before being used to perform PGx studies in patients, in order to confirm that they are adequate for the intended purposes., Methods: We designed a validation process for our in-house pharmacogenetic PCR-based method assay., Results: The concordance to reference, repeatability and reproducibility was 100%. Sensitivity and specificity were 100% for the detection of variant diplotypes in CYP2C9, CYP3A5, TPMT, DPYD and UGT1A1 genes. The sensitivity was lower in the detection of CYP2C19 variants due to a limitation in the design that prevents the detection of CYP2C19 *2/*10 diplotype., Conclusions: The success of implementing clinical pharmacogenetic testing into routine clinical practice is dependent on the precision of genotyping. Limitations must be bearing in mind to guarantee the quality of PGx assays in clinical laboratory practice. We provided objective evidence that the necessary requirements in our laboratory-development assay were fulfilled., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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15. Novel SLC12A2-ROS1 Fusion in Non-Small Cell Lung Cancer with a Significant Response to Crizotinib: The Importance of Choosing the Appropriate Next-Generation Sequencing Assay.
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Rodríguez-Antolín C, Rosas-Alonso R, Cruz P, Higuera O, Sánchez-Cabrero D, Esteban-Rodríguez I, Peláez-García A, Fernández Montaño VE, Rodríguez-Jiménez C, Ibáñez de Cáceres I, and de Castro J
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- Crizotinib pharmacology, Crizotinib therapeutic use, High-Throughput Nucleotide Sequencing, Humans, In Situ Hybridization, Fluorescence, Oncogene Proteins, Fusion genetics, Protein-Tyrosine Kinases genetics, Proto-Oncogene Proteins genetics, Solute Carrier Family 12, Member 2, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics
- Abstract
Identifying the druggable target is crucial for patients with nonsquamous advanced non-small cell lung cancer (NSCLC). This article adds to the spectrum of ROS1 fusion cases described in NSCLC. We describe a novel SLC12A2-ROS1 rearrangement that has not been previously reported in other cancers: a fusion that has clinical and radiological sensitivity to crizotinib. Fluorescence in situ hybridization detected the SLC12A2-ROS1 fusion and it was confirmed through hybrid capture-based next-generation sequencing (NGS); however, the fusion could not be detected by amplicon-based assay. The success of implementing NGS into routine clinical practice depends on the accuracy of testing. The test's methodological features should then be considered because they significantly affect the results. Given this patient's response to crizotinib, identifying patients with undescribed ROS1 fusions has important therapeutic implications. KEY POINTS: This is the first known description of an SLC12A2-ROS1 fusion. Considering the patient's clinical features and tumor response observed after crizotinib therapy, the authors confirm that this new rearrangement has relevant clinical impact for patients with non-small cell lung cancer. The success of implementing next-generation sequencing (NGS) into routine clinical practice depends on the accuracy of the testing. Different assays and NGS platforms can achieve differing results. Each assay's limitations need to be considered to ensure the quality of precision medicine in clinical practice., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)
- Published
- 2021
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16. Symptomatic heterozygous X-Linked myotubular myopathy female patient with a large deletion at Xq28 and decrease expression of normal allele.
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Gómez-González C, Rosas-Alonso R, Rodríguez-Antolín C, García-Guede A, Ibáñez de Caceres I, Sanguino J, Pascual SI, Esteban I, Pozo AD, Mori MÁ, Torres RJ, and Prior C
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- Adaptor Proteins, Signal Transducing metabolism, Adolescent, Chromosomes, Human, X genetics, Female, Heterozygote, Humans, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Myopathies, Structural, Congenital metabolism, Myopathies, Structural, Congenital pathology, Nuclear Proteins metabolism, Protein Tyrosine Phosphatases, Non-Receptor metabolism, Tumor Suppressor Proteins metabolism, Adaptor Proteins, Signal Transducing genetics, Chromosome Deletion, Myopathies, Structural, Congenital genetics, Nuclear Proteins genetics, Protein Tyrosine Phosphatases, Non-Receptor genetics, Tumor Suppressor Proteins genetics
- Abstract
X-linked myotubular myopathy (XLMTM; OMIM 310400) is a centronuclear congenital muscular disorder of X-linked recessive inheritance. Although female carriers are typically asymptomatic, affected heterozygous females have been described. Here, we describe the case of a sporadic female patient with suspicion of centronuclear myopathy and a heterozygous large deletion at Xq28 encompassing the MAMLD1, MTM1, MTMR1, CD99L2, and HMGB3 genes. The deletion was first detected using a custom next generation sequencing (NGS)-based multigene panel and finally characterized by comparative genomic hybridization array and multiplex ligation probe assay techniques. In this patient we have confirmed, by MTM1 mRNA quantification, a MTM1 gene expression less than the expected 50 percent in patient muscle. The significant 20% reduction in MTM1 mRNA expression in muscle, precludes low level of the normal myotubularin protein as the cause of the phenotype in this heterozygous female. We have also found that BIN1 expression in patient muscle biopsy was significantly increased, and postulate that BIN1 expression will be increased in XLMTM patient muscle as an attempt to maintain muscle function., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
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- 2021
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17. Clinical validation of a novel quantitative assay for the detection of MGMT methylation in glioblastoma patients.
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Rosas-Alonso R, Colmenarejo-Fernandez J, Pernia O, Rodriguez-Antolín C, Esteban I, Ghanem I, Sanchez-Cabrero D, Losantos-Garcia I, Palacios-Zambrano S, Moreno-Bueno G, de Castro J, Martinez-Marin V, and Ibanez-de-Caceres I
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- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Alkylating therapeutic use, Brain Neoplasms mortality, Cohort Studies, CpG Islands, DNA Methylation, DNA Modification Methylases genetics, DNA Repair Enzymes genetics, Epigenomics, Female, Glioblastoma drug therapy, Glioblastoma surgery, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Polymerase Chain Reaction methods, Polymerase Chain Reaction trends, Prognosis, Progression-Free Survival, Promoter Regions, Genetic genetics, Prospective Studies, ROC Curve, Sensitivity and Specificity, Temozolomide therapeutic use, Tumor Suppressor Proteins genetics, Biomarkers, Tumor genetics, Brain Neoplasms pathology, Glioblastoma diagnosis, Glioblastoma genetics
- Abstract
Background: The promoter hypermethylation of the methylguanine-DNA methyltransferase gene is a frequently used biomarker in daily clinical practice as it is associated with a favorable prognosis in glioblastoma patients treated with temozolamide. Due to the absence of adequately standardized techniques, international harmonization of the MGMT methylation biomarker is still an unmet clinical need for the diagnosis and treatment of glioblastoma patients., Results: In this study we carried out a clinical validation of a quantitative assay for MGMT methylation detection by comparing a novel quantitative MSP using double-probe (dp_qMSP) with the conventional MSP in 100 FFPE glioblastoma samples. We performed both technologies and established the best cutoff for the identification of positive-methylated samples using the quantitative data obtained from dp_qMSP. Kaplan-Meier curves and ROC time dependent curves were employed for the comparison of both methodologies., Conclusions: We obtained similar results using both assays in the same cohort of patients, in terms of progression free survival and overall survival according to Kaplan-Meier curves. In addition, the results of ROC(t) curves showed that dp_qMSP increases the area under curve time-dependent in comparison with MSP for predicting progression free survival and overall survival over time. We concluded that dp_qMSP is an alternative methodology compatible with the results obtained with the conventional MSP. Our assay will improve the therapeutic management of glioblastoma patients, being a more sensitive and competitive alternative methodology that ensures the standardization of the MGMT-biomarker making it reliable and suitable for clinical use.
- Published
- 2021
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18. Hypermethylation of Anti-oncogenic MicroRNA 7 is Increased in Emphysema Patients.
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Rosas-Alonso R, Galera R, Sánchez-Pascuala JJ, Casitas R, Burdiel M, Martínez-Cerón E, Vera O, Rodriguez-Antolin C, Pernía O, De Castro J, García-Rio F, and Ibanez-de-Cáceres I
- Subjects
- DNA Methylation, Humans, Prospective Studies, Emphysema, MicroRNAs genetics, Pulmonary Disease, Chronic Obstructive genetics
- Abstract
Introduction: MicroRNA-7 (miR-7) has a suppressive role in lung cancer and alterations in its DNA methylation may contribute to tumorigenesis. As COPD patients with emphysema have a higher risk of lung cancer than other COPD phenotypes, we compared the miR-7 methylation status among smoker subjects and patients with various COPD phenotypes to identify its main determinants., Methods: 30 smoker subjects without airflow limitation and 136 COPD patients without evidence of cancer were recruited in a prospective study. Clinical and functional characteristics were assessed and patients were classified into: frequent exacerbator, emphysema, chronic bronchitis and asthma COPD overlap (ACO). DNA collected from buccal epithelial samples was isolated and bisulfite modified. miR-7 methylation status was evaluated by quantitative methylation-specific polymerase chain reaction (qMSP)., Results: miR-7 Methylated levels were higher in COPD patients than in smokers without airflow limitation (23.7±12.4 vs. 18.5±8.8%, p=0.018). Among COPD patients, those with emphysema had higher values of methylated miR-7 (27.1±10.2%) than those with exacerbator (19.4±9.9%, p=0.004), chronic bronchitis (17.3±9.0%, p=0.002) or ACO phenotypes (16.0±7.2%, p=0.010). After adjusting for clinical parameters, differences between emphysematous patients and those with other phenotypes were retained. In COPD patients, advanced age, mild-moderate airflow limitation, reduced diffusing capacity and increased functional residual capacity were identified as independent predictors of methylated miR-7 levels., Conclusion: The increase of miR-7 methylation levels experienced by COPD patients occurs mainly at the expense of the emphysema phenotype, which might contribute to explain the higher incidence of lung cancer in these patients., (Copyright © 2019 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)
- Published
- 2020
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19. miR-7 methylation as a biomarker to predict poor survival in early-stage non-small cell lung cancer patients.
- Author
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Rodríguez-Antolín C, Felguera-Selas L, Pernía O, Vera O, Esteban I, Losantos García I, de Castro J, Rosas-Alonso R, and Ibanez de Caceres I
- Abstract
Non-small-cell lung cancer (NSCLC) is the most common malignancy worldwide. Platinum-based chemotherapy is the standard of care for these patients. Recent research showed that miR-7 methylation status is a biomarker of cisplatin resistance in lung and ovarian cancer cells, which is one of the major limitations associated with their clinical management. The aim of the present study is to provide clinical insights associated with this novel potential biomarker in NSCLC patients by comparing the miR-7 methylation status with the cisplatin treatment response. Our results analyzed in 81 samples show that miR-7 methylation is a common event in tumor tissue and it is more frequent as the stage of the disease advances, remaining in 75% of metastatic patients. Tumor miR-7 unmethylation trend to a better PFS in early stages, and when our data was validated in an extended " in silico" cohort of 969 patients we obtained a significant increment in PFS and OS in those patients harboring miR-7 unmethylated (p = 0.010 and p = 0.007 respectively). When we select those early-stages patients harbouring miR-7 methylation, we observed that adenocarcinoma patients present a dramatic decrease in PFS compared with squamous cell carcinoma patients (median 18.9 versus 59.7 months, p = 0.002). In conclusion, our results show that presence of miR-7 methylation in early-stage NSCLC is suggestive of aggressive behavior, especially for adenocarcinoma patients. One major challenge in early diagnosis in NSCLC is identify the subgroup of patients that could benefit for adjuvant therapy, our data establish the basis for epigenetic classification on early-stage NSCLC that could influence treatment decisions in the future., Competing Interests: Competing interestsThe authors declare that they have no competing interests.
- Published
- 2019
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- View/download PDF
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