miRNA expression profile in pediatric and adolescent and young adult rhabdomyosarcomas

Adolescents and young adults (AYA) with rhabdomyosarcoma (RMS) form a subgroup of patients whose optimal clinical management and best possible access to care remain a challenge and survival lacks behind that of children while diagnosed with histologically similar tumors. Understanding the tumor biology that differentiate children from AYA-RMS could provide critical information and drive new initiatives to improve their final outcome. MiRNA profile was evaluated in a RMS series of 49 tumor and 13 non-neoplastic tissues. MiRNAs analysis identified miR-223 over-expression and mir-431 down-regulation in AYA, validated by Real-Time PCR and miRNA ISH. A cohort of 49 RMS FFPE (formalin fixed paraffin embedded) tissues (not pre-treated primary tumors) was carefully selected and retrieved from the archive of Fondazione IRCCS Istituto Nazionale dei Tumori and were re-evaluated by expert pathologists for abundance and adequacy of material. Non-neoplastic components were identified where possible for each age groups of RMS,as controls in bioinformatic analyses. In details, RNA was successfully isolated from 27 pediatric RMS (0-14 years) and 22 AYA RMS (15-+30 years). Two samples (FF62 and FG07) were used as controls for adjacent normal tissues; the remaining 49 tumors and 13 normal conterpart was used for the analysis. MiRNA profile using a SurePrint G3 Human miRNA r21 microarray on miRBAse 21.0 (miRNA) Agilent (~ 2.000 miRNA) was successfully performed. When possible the normal tissue was obtained by a FFPE tissue block different from that of the tumor; otherwise, the pathologist selected a normal tissue area next to the tumor. The former was defined "normal", the latter "adjacent_normal".