IP: Dr. Andrés García Montero / Dr. Luis Escribano Mora

Resumen del proyecto: Systemic Mastocytosis (SM) is a rare which makes difficult to obtain a large number of patients. SM has heterogeneous clinical appearance, from indolent (ISM) forms with normal live expectation to very aggressive, life-threatening, disease (ASM). Despite of this, D816V activating c-KIT mutation is present in the majority os SM patients independently of their severity. Thus, secondary genetic alterations are thought to be cause of the disease progression to the most aggressive cases. Objective: to identify genetic alterations, secondary to D816V mutation, within the exome of SM patients who have progressed from indolent to aggressive forms of the disease, and to know the amount of infiltration these mutation could have in the hematopoiesis of SM patients with different forms of SM, to establish their importance in the severity and progression of the disease. Patients will be diagnosed and controlled by the Spanish network on mastocitosis (REMA). All of them will give their approval, by signing a specific (inform) consent, to participate in this project. Also healthy subjects with same age and gender will be used as controls. Methods: Whole exome sequencing, using NGS methods, of DNA samples for a panel of 409 cancer genes (Ion Proton, Life Technologies) from a group of MSA patients representatives of those who progress from indolent forms. In a second step the most relevant mutations found will tested in circulating DNA obtained from plasma samples of selected SM patients and controls. Detection will be performed using a real time PCR approach. Analysis of the correlation between sequencing, immunophenotypic and molecular data, along with the associated clinical and environmental features will allow us identify those mutations which could improve the diagnostic and prognostic criteria to predict a potential disease progression.

Entidad financiadora: Fundación Ramón Areces / Fundación Samuel Solórzano