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Integrative genetic profile and identification diagnostic markers
In order to achieve the complete global genetic landscape of these rare tumors we are studying the molecular profile of poorly characterized Non-Hodgkin lymphoma subtypes by high resolution techniques. Moreover, in order to go deep into the biology of these tumors and to identify age or refractoriness related markers, we are molecularly analyzing large retrospective series of pediatric and young adult NHL subtypes, including both immuncompetent patients and patients with postransplant lymphoproliferative disorder, with complete clinical data available in collaboration with Sociedad Española de Hematología y Oncología Pediátricas-SEHOP.
Study of intratumoral heterogeneity
Data already obtained in the analysis of pediatric NHL shows the presence of intratumoral heterogeneity that may represent the existence of different subclones. Although there are studies of the mutational hierarchy in adult NHL series, there is no approach in pediatric tumors. We aim to establish the mutational hierarchy in pediatric lymphoma types and determine the relationship between the presence of these mutations and histological areas corresponding to different morphological compartments by implementing different analysis pipelines and establishing in situ mutational detection probes.
Also we attempt, after generation of the necessary cryopreserved tissue collection, to set up in the lab single-cell techniques that could be applied to pediatric NHL tissue samples.
Identification of genetic biomarkers and drug targets
Our final goal is to identify target genes/pathways that can be useful biomarkers in the management of pediatric NHL. In detail, we aim to identify markers that can contribute in the design of more adapted therapies, improve the stratification of patients according to risk (markers associated with relapse/refractoriness) or markers whose presence/absence identify patients who do not need treatment or may be possible to de-escalate the chemotherapy doses of current protocols. Moreover, function of specific deregulated genes can be modified using drugs, opening the door to more effective therapies.
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