Abstract 970: Circulating microRNA signature in group 4 medulloblastoma patients
Authors: Miele Evelina , Alfano Vincenzo , Besharat Zein Mersini , Catanzaro Giuseppina , Mastronuzzi Angela , Carai Andrea , Po Agnese , Abballe Luana , Cacchione Antonella , Locatelli Franco , Ferretti Elisabetta 
Published: July 2016

Medulloblastoma is the most common malignant brain tumor in childhood. Four main clinically and molecularly distinct MB subtypes have been identified: WNT, SHH, Group 3, and Group 4. Among them, Group 4 MB (G4MB) appears to have the most skewed age ratio, is predominant in males and shows an intermediate prognosis. In spite of being the most frequent (35%), it is also the least understood of all the subgroups. Diagnosis is based on patients’ clinical symptoms and neuro-imaging techniques with high risk of false positive and/or late tumor discovery. The early detection of the disease is essential to reduce both cancer mortality and long time therapy related toxicity. To date, there is no reliable marker for G4MB that could facilitate the early diagnosis and allow the evaluation of the response to radio and chemotherapy treatment. Therefore, the discovery of new biomarkers as a specific signature of G4MB patients, potentially useful as diagnostic factor, would be extraordinarily worthwhile.

MicroRNAs are single-stranded non coding RNA molecules of 19-24 nucleotides in length involved in the post-transcriptional regulation of gene expression, whose expression is strongly deregulated in several types of tumors. Recent studies have shown that microRNAs are released into the bloodstream and are stably detectable thanks to their association with extracellular vescicle, or complex with RNA-binding protein that protect them from RNAse degradation. The minimally invasive liquid biopsy flanked to the reliability and specificity of microRNAs in cancer detection indicates circulating microRNAs not only as promising biomarkers to get early diagnosis, but also to follow treatment response and detect recurrence.

Here we report a high-throughput screening of microRNAs in G4MB plasma samples before surgery and during follow-up. Two different approaches (DeepSeq and Low Denstity Array) were used to detect the differentially expressed circulating microRNAs in 4 patients and in 4 age- and sex- matched healthy donors. Baseline microRNA expression profiling allowed us to disclose a signature of 34 miRNAs able to identify patients versus healthy children. Moreover, selected microRNAs were validated by RT-qPCR technology on a wider cohort of G4MB patients (n = 8) and healthy donors (n = 8). Specifically, we identified two important oncogenic microRNA clusters (miR-17/92 and miR-106b/25) significantly upregulated in G4MB plasma patients. Therapy reduced the expression of these microRNAs up to levels of healthy donors.

In conclusion we identified circulating microRNA signature in G4MB.

Citation Format: Evelina Miele, Vincenzo Alfano, Zein Mersini Besharat, Giuseppina Catanzaro, Angela Mastronuzzi, Andrea Carai, Agnese Po, Luana Abballe, Antonella Cacchione, Franco Locatelli, Elisabetta Ferretti. Circulating microRNA signature in group 4 medulloblastoma patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 970.