Ricerc@Sapienza

Tumors of the central nervous system (CNS) represent the second most common pediatric cancer (1). Medulloblastoma (MB), a pathology with high risk of relapse and no circulating biomarker available, is the most common malignant brain tumor occurring in childhood. MB has been distinct in 4 molecular subgroups (WNT, SHH, Group 3 and Group 4), characterized by distinct transcriptional, cytogenetic, patient demographics and clinical behavior (2). Among subgroups, SHH, Group 3 and 4 often recur with poor outcome (3). The identification of MB patients at high risk of recurrence and the early detection of recurrence itself, are critical for informed patient management decisions.
The aim of this project is to investigate miRNAs that can be exploited as biomarkers during follow-up, for the critical early detection of relapse. Since it has been shown that miRNAs can be found in body fluids, we plan to analyze circulating miRNAs from MB patients. To this end miRNA expression profiles of MB samples and of plasma samples derived from the same patients at the time of primary diagnosis, after surgery and in case of recurrence will be evaluated. To better define MB specific miRNAs we will analyze miRNA profiles by Next Generation Sequencing (NGS). Final purpose of the present research plan will be to identify deregulated miRNAs detectable in plasma samples and to identify those miRNAs with a role as disease biomarkers both at diagnosis and relapse in order to improve prognostic accuracy and better guide management clinicians decisions in MB.

1. Arora et al,(2009)Age-incidence patterns of primary CNS tumors in children, adolescents, and adults in England. Neuro Oncol.
2. Northcott et al,(2012)Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples. Acta Neuropath.
3. Ramaswamy et al,(2013)Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol.