Nuestros investigadores

Marta Fernández Mercado

Publicaciones científicas más recientes (desde 2010)

Autores: Aguilera Díaz, Almudena; Vázquez Urio, Iria; Ariceta, B.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 15  Nº 1  2020  págs. e0227986
The diagnosis of myeloid neoplasms (MN) has significantly evolved through the last few decades. Next Generation Sequencing (NGS) is gradually becoming an essential tool to help clinicians with disease management. To this end, most specialized genetic laboratories have implemented NGS panels targeting a number of different genes relevant to MN. The aim of the present study is to evaluate the performance of four different targeted NGS gene panels based on their technical features and clinical utility. A total of 32 patient bone marrow samples were accrued and sequenced with 3 commercially available panels and 1 custom panel. Variants were classified by two geneticists based on their clinical relevance in MN. There was a difference in panel¿s depth of coverage. We found 11 discordant clinically relevant variants between panels, with a trend to miss long insertions. Our data show that there is a high risk of finding different mutations depending on the panel of choice, due both to the panel design and the data analysis method. Of note, CEBPA, CALR and FLT3 genes, remains challenging the use of NGS for diagnosis of MN in compliance with current guidelines. Therefore, conventional molecular testing might need to be kept in place for the correct diagnosis of MN for now.
Autores: Aguilera-Diaz, A.; Larráyoz Ilundáin, María José; Palomino-Echeverria, S.; et al.
Revista: LEUKEMIA RESEARCH
ISSN 0145-2126  Vol. 95  2020 
Myeloid neoplasms (MN) are usually sporadic late-onset cancers; nevertheless, growing evidence suggests that similar to 5% of the cases could emerge as a consequence of inherited predisposition. Distinguishing somatic from germline variants is of vital importance, in order to establish an appropriate individualized management and counsel the patients and their relatives. Since many of the genes associated with myeloid neoplasm germline predisposition (MNGP) are also affected in sporadic MN, we intended to design a strategy to identify potentially inherited variants in a tumor only NGS panel in a cohort of 299 patients with a variety of MN. We considered as indicative of potential inherited origin, variants detected in BM sample at a similar to 50% VAF classified as pathogenic, likely pathogenic or of unknown significance detected in MNGP-related genes. A total of 104 suspicious variants from 90 patients were filtered-in in tumor samples. Mutational patterns, follow-up data, and sequencing of a range of non-myeloid tissues were used for narrowing down the list of suspicious variants, and ultimately discriminate their nature. Our data supports the importance of considering variants found upon tumor-only sequencing as potentially of germline origin, and we offer a pipeline to define the nature of the variants.
Autores: Palomo, L.; Ibáñez, M.; Abáigar, M.; et al.
Revista: BRITISH JOURNAL OF HAEMATOLOGY
ISSN 0007-1048  2019 
The landscape of medical sequencing has rapidly changed with the evolution of next generation sequencing (NGS). These technologies have contributed to the molecular characterization of the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), through the identification of recurrent gene mutations, which are present in >80% of patients. These mutations contribute to a better classification and risk stratification of the patients. Currently, clinical laboratories include NGS genomic analyses in their routine clinical practice, in an effort to personalize the diagnosis, prognosis and treatment of MDS and CMML. NGS technologies have reduced the cost of large-scale sequencing, but there are additional challenges involving the clinical validation of these technologies, as continuous advances are constantly being made. In this context, it is of major importance to standardize the generation, analysis, clinical interpretation and reporting of NGS data. To that end, the Spanish MDS Group (GESMD) has expanded the present set of guidelines, aiming to establish common quality standards for the adequate implementation of NGS and clinical interpretation of the results, hoping that this effort will ultimately contribute to the benefit of patients with myeloid malignancies.
Autores: Ariceta-Ganuza, B.; Aguilera Díaz, Almudena; Vázquez Urio, Iria; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 104  Nº S3  2019  págs. 174 - 174
Autores: Riego Repullo, Victoria; Blasco-Iturri, Z. ; Villar Fernández, Sara; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 104  Nº S3  2019  págs. 110 - 111
Autores: Aguirre-Ruiz, P. ; Viguria, M. C.; Blasco-Iturri, Z. ; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 104  Nº S3  2019  págs. 329 - 330
Autores: Blasco-Iturri, Z.; Vázquez Urio, Iria; Ariceta, B.; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 104  Nº S3  2019  págs. 56 - 57
Autores: Ariceta-Ganuza, B.; Mañú Arruti, Amagoia; Larráyoz Ilundáin, María José; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 104  Nº S3  2019  págs. 249 - 249
Autores: Aguilera Díaz, Almudena; Vázquez Urio, Iria; Ariceta, B.; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 104  Nº S3  2019  págs. 110 - 110
Autores: Prieto-Conde, M. I. ; Vázquez Urio, Iria; Fernández Mercado, Marta; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 104  Nº S3  2019  págs. 266 - 266
Autores: Aguilera Díaz, Almudena; Palomino-Echeverria, S.; Vázquez Urio, Iria; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 104  Nº S3  2019  págs. 72 - 73
Autores: Fernández Mercado, Marta; Larráyoz Ilundáin, María José; Vázquez Urio, Iria; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 102  Nº Supl. 2  2017  págs. 46 - 46
Autores: Pellagatti, A.; Roy, S.; Di Genua, C.; et al.
Revista: LEUKEMIA
ISSN 0887-6924  Vol. 30  Nº 1  2016  págs. 247 - 250
Autores: Pellagatti, A.; Fernández Mercado, Marta; Di Genua, C.; et al.
Revista: LEUKEMIA
ISSN 0887-6924  Vol. 28  Nº 5  2014  págs. 1148 - 1151
Autores: Fernández Mercado, Marta; Pellagatti, A.; Di Genua, C.; et al.
Revista: BRITISH JOURNAL OF HAEMATOLOGY
ISSN 0007-1048  Vol. 163  Nº 2  2013  págs. 235 - 239
Whole exome sequencing was performed in a patient with myelodysplastic syndrome before and after progression to acute myeloid leukaemia. Mutations in several genes, including SETBP1, were identified following leukaemic transformation. Screening of 328 patients with myeloid disorders revealed SETBP1 mutations in 14 patients (4 center dot 3%), 7 of whom had -7/del(7q) and 3 had i(17)(q10), cytogenetic markers associated with shortened overall survival and increased risk of leukaemic evolution. SETBP1 mutations were frequently acquired at the time of leukaemic evolution, coinciding with increase of leukaemic blasts. These data suggest that SETBP1 mutations may play a role in MDS and chronic myelomonocytic leukaemia disease progression.
Autores: Pérez, C.; Martínez Calle, Nicolás; Martín Subero, J. I.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 7  Nº 2  2012  págs. e31605
Chronic myelomonocytic leukemia (CMML) has recently been associated with a high incidence of diverse mutations in genes such as TET2 or EZH2 that are implicated in epigenetic mechanisms. We have performed genome-wide DNA methylation arrays and mutational analysis of TET2, IDH1, IDH2, EZH2 and JAK2 in a group of 24 patients with CMML. 249 genes were differentially methylated between CMML patients and controls. Using Ingenuity pathway analysis, we identified enrichment in a gene network centered around PLC, JNK and ERK suggesting that these pathways, whose deregulation has beenrecently described in CMML, are affected by epigenetic mechanisms. Mutations of TET2, JAK2 and EZH2 were found in 15 patients (65%), 4 patients (17%) and 1 patient (4%) respectively while no mutations in the IDH1 and IDH2 genes were identified. Interestingly, patients with wild type TET2 clustered separately from patients with TET2 mutations, showed a higher degree of hypermethylation and were associated with higher risk karyotypes. Our results demonstrate the presence of aberrant DNA methylation in CMML and identifies TET2 mutant CMML as a biologically distinct disease subtype with a different epigenetic profile.
Autores: Fernández Mercado, Marta; Yip, B. H.; Pellagatti, A.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 7  Nº 8  2012  págs. e42334
Acute myeloid leukemia patients with normal cytogenetics (CN-AML) account for almost half of AML cases. We aimed to study the frequency and relationship of a wide range of genes previously reported as mutated in AML (ASXL1, NPM1, FLT3, TET2, IDH1/2, RUNX1, DNMT3A, NRAS, JAK2, WT1, CBL, SF3B1, TP53, KRAS and MPL) in a series of 84 CN-AML cases. The most frequently mutated genes in primary cases were NPM1 (60.8%) and FLT3 (50.0%), and in secondary cases ASXL1 (48.5%) and TET2 (30.3%). We showed that 85% of CN-AML patients have mutations in at least one of ASXL1, NPM1, FLT3, TET2, IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations; seventeen cases presented mutations of at least one of these genes. However, there was no consistent pattern in mutation acquisition during disease progression. This report concerns the analysis of the largest number of gene mutations in CN-AML studied to date, and provides insight into the mutational profile of CN-AML.
Autores: Boultwood, J.; Perry, J.; Pellagatti, A.; et al.
Revista: LEUKEMIA
ISSN 0887-6924  Vol. 24  Nº 5  2010  págs. 1062 - 1065