Characterization of genetic and epigenetic events in primary and recurrent pediatric high grade gliomas.

Proponente Manila Antonelli - Professore Associato
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca

Glial tumours in children have distinct patterns of epigenetic alteration, chromosomal structure, and gene and protein expression that differentiate them from their histological counterparts in adults. Understanding paediatric gliomas at the molecular level provides important prognostic and therapeutic insights.
High grade gliomas (HGG) account for 15% of all pediatric brain tumors and their outcome remains dismal.
Recently it has been described the involvement of multiple epigenetic regulatory processes by affecting histone modification, DNA methylation, and chromatin remodeling. Moreover in recent years microRNAs (miRNAs), acting either as oncogenes or tumor suppressor genes, have also been identified. Distally recurred/metastatic glioblastoma in adult shared only a minority of initial tumor mutations, indicative of divergent evolution. In contrast, most of locally recurred tumors shared a majority of initial tumor mutations, consistent with linear evolution. These observations implicated that an effective therapy for the primary tumor would be ineffective for the recurrent lesions. Such knowledge is missing for pediatric HGG. The aim of the project is to determine genomic and epigenomic divergences between the primary and recurrent tumors.
Moreover a variant of pHGG is diffuse intrinsic pontine glioma (DIPG), a brainstem malignancy with a median survival of Understanding biologic differences that confer survival advantage in DIPG paves the road toward development of subgroup-specific therapies that, when implemented in the context of clinical trials, may improve outcomes for this devastating disease .
This project requires knowledge in molecular biology of microRNA molecules, sequencing technologies and in neuropathology and neurooncology.

LS2_5, LS1_10, LS2_6

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