Abstract

Medulloblastoma is a highly aggressive brain tumor that typically affects children, while in adults it represents ~1% of all brain tumors. Little is known about microRNA expression profile of the rare adult medulloblastoma. The main aim of this study was to identify peculiar differences in microRNA expression between childhood and adult medulloblastoma. Medulloblastomas were profiled for microRNA expression using the Exiqon Human miRNome panel (I + II) analyzing 752 microRNAs in a training set of six adult and six childhood cases. Then, the most differentially expressed microRNAs were validated in a total of 21 adult and 19 childhood cases. Eight microRNAs (miR-196b-5p, miR-183-5p, miR-200b-3p, miR-196a-5p, miR-193a-3p, miR-29c-3p, miR-33b-5p, and miR-200a-3p) were differentially expressed in medulloblastoma of adults and children. Analysis of the validation set confirmed that miR-196b-5p and miR-200b-3p were significantly overexpressed in medulloblastoma of adults as compared with those of children. We followed an in silico approach to investigate direct targets and the pathways involved for the two microRNAs (miR-196b and miR-200b) differently expressed between adult and childhood medulloblastoma. Adult and childhood medulloblastoma have different miRNA expression profiles. In particular, the differential dysregulation of miR-196b-5p and miR-200b-3p characterizes the miRNA profile of adult medulloblastoma and suggests potential targets for novel diagnostic, prognostic, or therapeutic strategies.

Highlights

  • Medulloblastoma (MB) represents about 10% of pediatric brain tumors in children from birth to 14 years old [1,2,3], with the highest incidence in children aged three to ten years [4]

  • We identified peculiar differences in miRNA expression between childhood and adult tumors, and we showed that miR-196b-5p and miR-200b-3p are significantly overexpressed in MB of adults

  • All experiments were approved by the review board, and they were carried out following relevant guidelines and regulations (CE: 09113)

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Summary

Introduction

Medulloblastoma (MB) represents about 10% of pediatric brain tumors in children from birth to 14 years old [1,2,3], with the highest incidence in children aged three to ten years [4]. MB in adults (patients ≥ 16 years of age) represents about 1% of all adult brain tumors [4,5,6]. The difference in the incidence between adults and children suggests distinct origins and tumorigenic mechanisms. Many studies have confirmed that MBs in adults and children are different types of tumors regarding their histology, localization, genetic landscape, and risk stratification [7,8,9,10,11]. This classification was incorporated into the latest World Health Organization (WHO) Classification of Tumors of the Central Nervous System [12] and has become a widely accepted criterion for MB diagnosis and to direct specific therapeutic strategies [12,13]

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