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12p11.21, 12p13.31, 16p11.2, 16q24.3, 17q21.31, 20p11.2 and 20p13. The 75 modulatorsplay an important role in ULs pathogenesis regardless of tumor multiplicity and menstrualcycle phase.The integrative analysis allowed the identification of 75 modulators based on geneexpression data and then generates the association of these findings with genomic imbalances.Forty-five out of 75 modulators have shown an inverse association between genomicalterations (gains or losses) and gene expression pattern (up- or down-regulation). Severalmechanisms, besides CNAs, are associated with gene expression regulation. Epigeneticmechanisms and miRNAs, for example, can regulate transcriptional events. Gene expressionregulation by miRNAs has been a major focus in studies of tumors, including ULs [33, 34]. Inthe present study, 30 out of 45 genes that showed an inverse association betweengenomic/transcriptomic data could be explained by miRNA regulation. The additional 15genes could be regulated by other mechanisms. In addition, 44 out of 75 modulators aremapped on chromosomal regions that generally are not frequent targets of breakpoints.Therefore, this study suggests that deregulated expression genes in ULs frequently areassociated with genomic alterations and regulation by miRNAs. Altogether, CNAs andmiRNA could explain the main mechanisms of regulation of gene expression of ULs samples.Based on Akavia et al. [17], it was selected 30 modulators showing the highest scoresvalues with 14 of them showing positive association (CALCRL, COL3A1, CTDSP1, DBN1,DIP2C, FGFR1, GPR4, HSPB7, IGFBP5, MFAP5, NUPR1, and TNS1) or negativeassociation (CENPF and RHOH). The TNS1, HSPB7, IGFBP5, GPR4 and CTDSP1modulators were not detected in modules, indicating that they could be classified into a newclass of genes specifically associated with ULs. These selected modulators genes could beputative candidates to uterine leiomyomas development and are discussed below.11