MicroRNA expression in sporadic and FAP-associated Desmoid Tumors and correlation with beta-catenin gene mutations

Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. MicroRNAs (miRNAs) are involved in many human carcinogenesis. The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFEP) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one miRNAs were dysregulated, of which 98 miRNAs in sporadic DTs, 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The same qPCR method was used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, miR-21-3p targets, and L1 Cell Adhesion Molecule, miR-197-3p target, was also evaluated. CTNNB1 mutations associated to miRNA dysregulation could help histological diagnosis of sporadic DTs and could affect the genesis and the progression of this disease. To define a specific DT miRNA profile, miRNA microarray analysis on FFEP tissue samples of 8 sporadic DTs, 4 FAP-associated DTs, regardless to tumor site, and 4 control samples has been performed. After evaluation of the CTNNB1 mutational status in 23 sporadic DTs, the altered miRNA expression pattern has been correlated with mutated (M) and wild-type (Wt) sporadic DTs.