List of communications


Detection of IDH1 mutations within circulating EVs from GBM patients

Esteban-Rubio Susana, Universidad San Pablo CEU, Madrid, Spain; Carrión-Navarro Josefa, Fundación Hospital de Madrid-IMMA, Madrid, Spain; García-Romero Noemí, IMDEA Nanoscience, Madrid, Spain; Zafra-Villaverde Antonio, Universidad San Pablo CEU, Madrid, Spain; Prat-Acín Ricardo, Hospital Universitario la Fe, Valencia, Spain; Fernández-Carballal Carlos, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Belda-Iniesta Cristobal, Fundación Hospital de Madrid-IMMA, Madrid, Spain, IMDEA Nanoscience, Madrid, Spain; Ayuso-Sacido Angel, Fundación Hospital de Madrid-IMMA, Madrid, Spain, IMDEA Nanoscience, Madrid, Spain, Universidad San Pablo-CEU, Madrid, Spain.


BACKGROUND

Diffuse gliomas are the most common malignant primary tumors, and Glioblastoma (WHO grade IV) is the most frequent diffuse glioma with a median patient survival of 15 months after diagnosis. Temozolomide (TMZ) and radiotherapy is currently the first-line of treatment for this disease, however, survival remains poor among these patients because of resistance to TMZ. The identification and validation of biomarkers for prosgnostic and respond to therapy value, using minimally invasive approaches, along the course of the disease, will significally improve the management of these tumors. In this sense, glioma cell extracellular vesicles (EVs) containing mRNA, gDNA or proteins, can cross the Blood Brain Barrier reaching the peripheral blood, from where they can be isolated and their cargo analysed. Somatic mutations at codon 132 of the isocitrate dehydrogenase 1 gene (IDH1) have been identified in approximately 12% of glioblastomas. This subgroup of patients display better prognostic, with improved overall survival. Our group have recently detected IDH1 gDNA sequences within EVs isolated from either tumor cells or EVs isolated from peripheral blood of athymic mice xenografted with cancer-initiating cells.

RESULTS AND CONCLUSION

We have studied the IDH1 sequence of EVs-isolated gDNA of peripheral blood samples from patients diagnosed with different degree of gliomas, together with controls. The results were validated by analysing the IDH1 sequence within the counterpart paraffin-embedded solid tumor specimens. Here we show a proof of concept for the use of the IDH1 mutations within peripheral blood EVs, as a prognostic biomarker via a minimally invasive technique.

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