Nuestros investigadores

Francisco Javier Novo Villaverde

Bioquímica y Genética
Facultad de Ciencias. Universidad de Navarra
Departamento de Bioquímica y Genética
Facultad de Ciencias. Universidad de Navarra
Índice H
17, (WoS, 25/03/2014)
17, (WoS, 20/01/2015)

Publicaciones científicas más recientes (desde 2010)

Autores: Eder-Azanza, L., ; Hurtado Rudi, Cristina; Navarro-Herrera, D., ; et al.
ISSN 0390-6078  Vol. 102  Nº 8  2017  págs. e328 - e331
Autores: Novo Villaverde, Francisco Javier
ISSN 2300-7648  Vol. 4  Nº 2  2016  págs. 97 - 114
I review Mariano Artigas' appraisal of Evolution as reflected in some of his works. I find that his perception of evolutionary theory changed from a critical attitude, mainly directed against the modern synthesis of the twentieth century, to a more lenient approach as he incorporated new elements into his reflections. However, he did not fully appreciate some of the advances made in evolutionary biology in recent years. I provide some examples, taken from the field of evolutionary genomics, which shed new light on why evolvability is a necessary property of living beings and how adaptation proceeds through the rewiring of modular gene regulatory networks, resulting in a remarkable degree of phenotypic plasticity. This view provides a richer understanding of two key elements of Artigas' portrayal of the modern worldview: dynamism and patterning.
Autores: Erquiaga Martínez, Ignacio; Hurtado Rudi, Cristina; Aranaz Oroz, Paula; et al.
ISSN 0736-6205  Vol. 56  Nº 6  2014  págs. 327 - 329
When studying mutations in DNA samples, determining whether novel sequence changes are somatic mutations or germline polymorphisms can be difficult. Here we describe a novel and very simple approach for identification of somatic mutations and loss of heterozygosity (LoH) events in DNA samples where no matched tissue sample is available. Our method makes use of heterozygous polymorphisms that are located near the putative mutation to trace both germinal alleles.
Autores: Eder Azanza, L., ; Navarro Herrera, D., ; Aranaz Oroz, Paula; et al.
ISSN 0887-6924  Vol. 28  Nº 10  2014  págs. 2106 - 2109
Autores: Shugay, M., ; Ortiz de Mendibil Ayuso, Íñigo; Vizmanos Pérez, José Luis; et al.
ISSN 1367-4803  Vol. 29  Nº 20  2013  págs. 2539 - 2546
Motivation: Gene fusions resulting from chromosomal aberrations are an important cause of cancer. The complexity of genomic changes in certain cancer types has hampered the identification of gene fusions by molecular cytogenetic methods, especially in carcinomas. This is changing with the advent of next-generation sequencing, which is detecting a substantial number of new fusion transcripts in individual cancer genomes. However, this poses the challenge of identifying those fusions with greater oncogenic potential amid a background of 'passenger' fusion sequences. Results: In the present work, we have used some recently identified genomic hallmarks of oncogenic fusion genes to develop a pipeline for the classification of fusion sequences, namely, Oncofuse. The pipeline predicts the oncogenic potential of novel fusion genes, calculating the probability that a fusion sequence behaves as 'driver' of the oncogenic process based on features present in known oncogenic fusions. Cross-validation and extensive validation tests on independent datasets suggest a robust behavior with good precision and recall rates. We believe that Oncofuse could become a useful tool to guide experimental validation studies of novel fusion sequences found during next-generation sequencing analysis of cancer transcriptomes.
Autores: Aranaz Oroz, Paula; Miguéliz Basterra, Itziar; Hurtado Rudi, Cristina; et al.
ISSN 1042-8194  Vol. 54  Nº 2  2013  págs. 428 - 431
Autores: Aranaz Oroz, Paula; Hurtado Rudi, Cristina; Erquiaga Martínez, Ignacio; et al.
Revista: Haematologica-journal of Hematology
ISSN 1138-0381  Vol. 97  Nº 8  2012  págs. 1234 -1241
Autores: Shugay, M., ; Ortiz de Mendibil Ayuso, Íñigo; Vizmanos Pérez, José Luis; et al.
ISSN 1553-7358  Vol. 8  Nº 12  2012  págs. e1002797
Reciprocal chromosomal translocations (RCTs) leading to the formation of fusion genes are important drivers of hematological cancers. Although the general requirements for breakage and fusion are fairly well understood, quantitative support for a general mechanism of RCT formation is still lacking. The aim of this paper is to analyze available high-throughput datasets with computational and robust statistical methods, in order to identify genomic hallmarks of translocation partner genes (TPGs). Our results show that fusion genes are generally overexpressed due to increased promoter activity of 5' TPGs and to more stable 3'-UTR regions of 3' TPGs. Furthermore, expression profiling of 5' TPGs and of interaction partners of 3' TPGs indicates that these features can help to explain tissue specificity of hematological translocations. Analysis of protein domains retained in fusion proteins shows that the co-occurrence of specific domain combinations is non-random and that distinct functional classes of fusion proteins tend to be associated with different components of the gene fusion network. This indicates that the configuration of fusion proteins plays an important role in determining which 5' and 3' TPGs will combine in specific fusion genes. It is generally accepted that chromosomal proximity in the nucleus can explain the specific pairing of 5' and 3' TPGS and the recurrence of hematological translocations. Using recently available data for chromosomal contact probabilities (Hi-C) we show that TPGs are preferentially located in early replicated regions and occupy distinct clusters in the nucleus. However, our data suggest that, in general, nuclear position of TPGs in hematological cancers explains neither TPG pairing nor clinical frequency. Taken together, our results support a model in which genomic features related to regulation of expression and replication timing determine the set of candidate genes more likely to be translocated in hematological tissues, with functional constraints being responsible for specific gene combinations.
Autores: Hurtado Rudi, Cristina; Erquiaga Martínez, Ignacio; Aranaz Oroz, Paula; et al.
Revista: Leukemia Research
ISSN 0145-2126  Vol. 35  Nº 11  2011  págs. 1537 - 1539
Autores: Salas Cintora, Elisa María; García Barchino, María José; Labiano Almiñana, Sara; et al.
Revista: Genes chromosomes & cancer (Print)
ISSN 1045-2257  Vol. 2  Nº 5  2011  págs. 593 - 596
Autores: Euba Rementeria, Begoña; Vizmanos Pérez, José Luis; García-Granero Marquez, Marta; et al.
Revista: Leukemia & Lymphoma
ISSN 1042-8194  Vol. 53  Nº 6  2011  págs. 1230-1233
Autores: Cristóbal Yoldi, Jon; Blanco, F. J., ; García-Orti, L., ; et al.
Revista: BLOOD
ISSN 0006-4971  Vol. 115  Nº 3  2010  págs. 615 - 625
Acute myeloid leukemias (AMLs) result from multiple genetic alterations in hematopoietic stem cells. We describe a novel t(12; 18)(p13;q12) involving ETV6 in a patient with AML. The translocation resulted in overexpression of SETBP1 (18q12), located close to the breakpoint. Overexpression of SETBP1 through retroviral insertion has been reported to confer growth advantage in hematopoietic progenitor cells. We show that SETBP1 overexpression protects SET from protease cleavage, increasing the amount of full-length SET protein and leading to the formation of a SETBP1 SET-PP2A complex that results in PP2A inhibition, promoting proliferation of the leukemic cells. The prevalence of SETBP1 overexpression in AML at diagnosis (n=192) was 27.6% and was associated with unfavorable cytogenetic prognostic group, monosomy 7, and EVI1 overexpression (P <.01). Patients with SETBP1 overexpression had a significantly shorter overall survival, and the prognosis impact was remarkably poor in patients older than 60 years in both overall survival (P=.015) and event-free survival (P=.015). In summary, our data show a novel leukemogenic mechanism through SETBP1 overexpression; moreover, multivariate analysis confirms the negative prognostic impact of SETBP1 overexpression in AML, especially in elderly patients, where it could be used as a predictive factor in any future clinical trials with PP2A activators.
Autores: Erquiaga Martínez, Ignacio; Ormazábal Goicoechea, Cristina; Hurtado Rudi, Cristina; et al.
ISSN 1042-8194  Vol. 51  Nº 9  2010  págs. 1720 - 1726
Hematological malignancies with eosinophilia are often associated with fusions in PDGFRA, PDGFRB, or FGFR1 genes. RT-PCR has proved to be useful for finding new PDGFRA gene fusions, but some studies have shown overexpression of the TK domain which cannot be explained by the existence of such aberrations. This fact could be related to the expression of alternative PDGFRA transcripts. We show that quantification of the expression of three different PDGFRA fragments discriminates between PDGFRA alternative transcripts and fusion genes, and we have tested this novel methodological approach in a group of eosinophilia cases. Our data show that alternative PDGFRA transcripts should be taken into account when screening for PDGFRA aberrations, such as gene fusions, by RT-PCR. Expression from an internal PDGFRA promoter seems to be a frequent event, in both normal and leukemic samples, and is probably related to physiological conditions, but it could have a role in other tumors. Even so, we show that our RQ-PCR methodology can discriminate expression of alternative transcripts from the presence of X-PDGFRA fusion genes.
Autores: Aranaz Oroz, Paula; Ormazábal Goicoechea, Cristina; Hurtado Rudi, Cristina; et al.
ISSN 0165-4608  Vol. 199  Nº 1  2010  págs. 1 - 8
BCR/ABL1-negative chronic myeloproliferative neoplasms (CMPNs) are a heterogeneous group of clonal hematological malignancies. Over recent years, some genetic events in tyrosine lcinase (TK) genes have been described as causal events of these diseases. To identify new genetic aberrations underlying these diseases, we used denaturing high performance liquid chromatography and fluorescence in situ hybridization (FISH) to analyze 17 genes from two receptor-TK families (III and IV) and from three cytoplasmic-TK families (Syk, Abl, and Jak) on samples from 44 BCR/ABL1-negative and JAK2(V617F)-negative CMPN patients with different clinical phenotypes. Although screening by FISH did not reveal novel chromosomal aberrations, several sequence changes were detected. None of them were frequent events, but we identified a new potential activating mutation in the FERM domain of JAK2(R340Q). None of the germline JAK2(V617F) singlenucleotide polymorphisms detected differed in distribution between patients and control subjects. In summary, data presented here show that these genes are not frequently mutated or rearranged in CMPNs, suggesting that molecular events causing these disorders must be located in other genes.
Autores: Novo Villaverde, Francisco Javier