6 results on '"Paula Melero Valentín"'
Search Results
2. Detection of new drivers of frequent B-cell lymphoid neoplasms using an integrated analysis of whole genomes.
- Author
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Adrián Mosquera Orgueira, Roi Ferreiro Ferro, José Ángel Díaz Arias, Carlos Aliste Santos, Beatriz Antelo Rodríguez, Laura Bao Pérez, Natalia Alonso Vence, Ággeles Bendaña López, Aitor Abuin Blanco, Paula Melero Valentín, And Res Peleteiro Raindo, Miguel Cid López, Manuel Mateo Pérez Encinas, Marta Sonia González Pérez, Máximo Francisco Fraga Rodríguez, and José Luis Bello López
- Subjects
Medicine ,Science - Abstract
B-cell lymphoproliferative disorders exhibit a diverse spectrum of diagnostic entities with heterogeneous behaviour. Multiple efforts have focused on the determination of the genomic drivers of B-cell lymphoma subtypes. In the meantime, the aggregation of diverse tumors in pan-cancer genomic studies has become a useful tool to detect new driver genes, while enabling the comparison of mutational patterns across tumors. Here we present an integrated analysis of 354 B-cell lymphoid disorders. 112 recurrently mutated genes were discovered, of which KMT2D, CREBBP, IGLL5 and BCL2 were the most frequent, and 31 genes were putative new drivers. Mutations in CREBBP, TNFRSF14 and KMT2D predominated in follicular lymphoma, whereas those in BTG2, HTA-A and PIM1 were more frequent in diffuse large B-cell lymphoma. Additionally, we discovered 31 significantly mutated protein networks, reinforcing the role of genes such as CREBBP, EEF1A1, STAT6, GNA13 and TP53, but also pointing towards a myriad of infrequent players in lymphomagenesis. Finally, we report aberrant expression of oncogenes and tumor suppressors associated with novel noncoding mutations (DTX1 and S1PR2), and new recurrent copy number aberrations affecting immune check-point regulators (CD83, PVR) and B-cell specific genes (TNFRSF13C). Our analysis expands the number of mutational drivers of B-cell lymphoid neoplasms, and identifies several differential somatic events between disease subtypes.
- Published
- 2021
- Full Text
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3. Gene expression profiling identifies FLT3 mutation-like cases in wild-type FLT3 acute myeloid leukemia.
- Author
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Adrián Mosquera Orgueira, Andrés Peleteiro Raíndo, Miguel Cid López, Beatriz Antelo Rodríguez, José Ángel Díaz Arias, Roi Ferreiro Ferro, Natalia Alonso Vence, Ángeles Bendaña López, Aitor Abuín Blanco, Laura Bao Pérez, Paula Melero Valentín, Marta Sonia González Pérez, Claudio Cerchione, Giovanni Martinelli, Pau Montesinos Fernández, Manuel Mateo Pérez Encinas, and José Luis Bello López
- Subjects
Medicine ,Science - Abstract
BackgroundFLT3 mutation is present in 25-30% of all acute myeloid leukemias (AML), and it is associated with adverse outcome. FLT3 inhibitors have shown improved survival results in AML both as upfront treatment and in relapsed/refractory disease. Curiously, a variable proportion of wild-type FLT3 patients also responded to these drugs.MethodsWe analyzed 6 different transcriptomic datasets of AML cases. Differential expression between mutated and wild-type FLT3 AMLs was performed with the Wilcoxon-rank sum test. Hierarchical clustering was used to identify FLT3-mutation like AMLs. Finally, enrichment in recurrent mutations was performed with the Fisher's test.ResultsA FLT3 mutation-like gene expression pattern was identified among wild-type FLT3 AMLs. This pattern was highly enriched in NPM1 and DNMT3A mutants, and particularly in combined NPM1/DNMT3A mutants.ConclusionsWe identified a FLT3 mutation-like gene expression pattern in AML which was highly enriched in NPM1 and DNMT3A mutations. Future analysis about the predictive role of this biomarker among wild-type FLT3 patients treated with FLT3 inhibitors is envisaged.
- Published
- 2021
- Full Text
- View/download PDF
4. Detection of Rare Germline Variants in the Genomes of Patients with B-Cell Neoplasms
- Author
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Adrián Mosquera Orgueira, Miguel Cid López, Andrés Peleteiro Raíndo, José Ángel Díaz Arias, Beatriz Antelo Rodríguez, Laura Bao Pérez, Natalia Alonso Vence, Ángeles Bendaña López, Aitor Abuin Blanco, Paula Melero Valentín, Roi Ferreiro Ferro, Carlos Aliste Santos, Máximo Francisco Fraga Rodríguez, Marta Sonia González Pérez, Manuel Mateo Pérez Encinas, and José Luis Bello López
- Subjects
germline ,rare variant ,cancer ,lymphoid ,B-cell ,lymphoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
There is growing evidence indicating the implication of germline variation in cancer predisposition and prognostication. Here, we describe an analysis of likely disruptive rare variants across the genomes of 726 patients with B-cell lymphoid neoplasms. We discovered a significant enrichment for two genes in rare dysfunctional variants, both of which participate in the regulation of oxidative stress pathways (CHMP6 and GSTA4). Additionally, we detected 1675 likely disrupting variants in genes associated with cancer, of which 44.75% were novel events and 7.88% were protein-truncating variants. Among these, the most frequently affected genes were ATM, BIRC6, CLTCL1A, and TSC2. Homozygous or germline double-hit variants were detected in 28 cases, and coexisting somatic events were observed in 17 patients, some of which affected key lymphoma drivers such as ATM, KMT2D, and MYC. Finally, we observed that variants in six different genes were independently associated with shorter survival in CLL. Our study results support an important role for rare germline variation in the pathogenesis and prognosis of B-cell lymphoid neoplasms.
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- 2021
- Full Text
- View/download PDF
5. Detection of Rare Germline Variants in the Genomes of B Cell Neoplasms
- Author
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Jose Luis Bello Lopez, Adrian Mosquera Orgueira, Roi Ferreiro Ferro, Miguel Cid López, José Ángel Díaz Arias, Beatriz Antelo Rodríguez, Laura Bao Pérez, Carlos Aliste Santos, Manuel Mateo Pérez Encinas, Natalia Alonso Vence, Ángeles Bendaña López, Maximo Francisco Fraga Martinez, Aitor Abuin Blanco, Paula Melero Valentín, Andrés Peleteiro Raíndo, and Marta Sonia González Pérez
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Genetics ,medicine.anatomical_structure ,allergology ,medicine ,Cancer ,Biology ,medicine.disease ,Genome ,Germline ,B cell - Abstract
Growing evidence has revealed the implication of germline variation in cancer predisposition and prognostication. Here, we describe an analysis of putatively disruptive rare variants across the genomes of 726 patients with B-cell lymphoid neoplasms. We discovered a significant enrichment of 26 genes in germline protein truncating variants (PTVs), affecting cell signaling (MET, JAK2, ANGPT2), energy metabolism (ACO1) and nucleic acid metabolism and repair pathways (NT5E, DCK). Interestingly, some of these variants were restricted to either chronic lymphocytic leukemia (CLL) (i.e., ANGPT2 and AKR1C3) or B-cell lymphoma cases (PNMT, TPT1 and IGHMBP2). Additionally, we detected 1,675 likely disrupting variants in genes associated with cancer, of which 44.75% were novel events and 7.88% were PTVs. Among these, the most frequently affected genes were ATM, BIRC6, CLTCL1A and TSC2. Homozygous or compound heterozygous variants were detected in 28 cases; and coexisting somatic events were observed in 17 patients, some of which affected key lymphoma drivers such as ATM, KMT2D and MYC. Finally, we observed that variants in the helicase gene WRN were independently associated with shorter survival in CLL. Our study results support an important role for rare germline variation in the pathogenesis, clinical presentation and disease outcome of B-cell lymphoid neoplasms.
- Published
- 2021
6. Gene expression profiling identifies FLT3 mutation-like cases in wild-type FLT3 acute myeloid leukemia
- Author
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Aitor Abuin Blanco, Ángeles Bendaña López, Adrián Mosquera Orgueira, Giovanni Martinelli, Andrés Peleteiro Raíndo, Laura Bao Pérez, Natalia Alonso Vence, José Luis Bello López, Marta Sonia González Pérez, Roi Ferreiro Ferro, Miguel Cid López, José Ángel Díaz Arias, Pau Montesinos Fernández, Claudio Cerchione, Paula Melero Valentín, Beatriz Antelo Rodríguez, and Manuel Mateo Pérez Encinas
- Subjects
Myeloid ,Mutant ,Cancer Treatment ,Gene Expression ,medicine.disease_cause ,DNA Methyltransferase 3A ,Hematologic Cancers and Related Disorders ,Database and Informatics Methods ,Mathematical and Statistical Techniques ,fluids and secretions ,hemic and lymphatic diseases ,Medicine and Health Sciences ,Cluster Analysis ,DNA (Cytosine-5-)-Methyltransferases ,Mutation ,Leukemia ,Multidisciplinary ,Nuclear Proteins ,Myeloid leukemia ,hemic and immune systems ,Hematology ,Genomics ,Myeloid Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Oncology ,embryonic structures ,Biomarker (medicine) ,Medicine ,Nucleophosmin ,Transcriptome Analysis ,Research Article ,Acute Myeloid Leukemia ,NPM1 ,Science ,Biology ,Research and Analysis Methods ,Genetics ,medicine ,Humans ,Hierarchical Clustering ,Gene Expression Profiling ,Cancers and Neoplasms ,Biology and Life Sciences ,Computational Biology ,Staurosporine ,Genome Analysis ,medicine.disease ,Gene expression profiling ,Biological Databases ,fms-Like Tyrosine Kinase 3 ,Mutation Databases ,Cancer research ,Biomarkers - Abstract
Background FLT3 mutation is present in 25–30% of all acute myeloid leukemias (AML), and it is associated with adverse outcome. FLT3 inhibitors have shown improved survival results in AML both as upfront treatment and in relapsed/refractory disease. Curiously, a variable proportion of wild-type FLT3 patients also responded to these drugs. Methods We analyzed 6 different transcriptomic datasets of AML cases. Differential expression between mutated and wild-type FLT3 AMLs was performed with the Wilcoxon-rank sum test. Hierarchical clustering was used to identify FLT3-mutation like AMLs. Finally, enrichment in recurrent mutations was performed with the Fisher’s test. Results A FLT3 mutation-like gene expression pattern was identified among wild-type FLT3 AMLs. This pattern was highly enriched in NPM1 and DNMT3A mutants, and particularly in combined NPM1/DNMT3A mutants. Conclusions We identified a FLT3 mutation-like gene expression pattern in AML which was highly enriched in NPM1 and DNMT3A mutations. Future analysis about the predictive role of this biomarker among wild-type FLT3 patients treated with FLT3 inhibitors is envisaged.
- Published
- 2021
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