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Visualizar Tese - Instituto de Biociências - Unesp

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mapped at 1p36.13, 1q41, 2q32.1, 2q32.2, 2q35, 4p14, 5q31.2, 5q35.3, 7q22.1, 8p12, 8q24.3,10p15.3, 10q21.3, 11p15.5, 11q13.2, 12p11.21, 12p13.31, 14q13.2, 16p11.2, 16q24.3,17q21.31, 19q13.32, 19q13.33, 20p11.2 and 20p13 (Table 1). The modulators had scoresranged from the 0 (TBC1D20 - TBC1 domain family, member 20) to 21227.32 (KIF20A -kinesin family member 20A).miRNA target prediction - Among the 75 modulators, 26 showed positive association(genomic gains/up-regulated) and three negative association (genomic losses/downregulated).An inverse correlation was found involving 45 genes and one ORF sequence(C8orf51); 30 of them could be explained by miRNA regulation (Table 1) (Table S3). ThemiRNA target prediction analysis was unable to predict the inverse correlation found in 15genes.Modulators characterization. Unsupervised hierarchical clustering analysis was donein or<strong>de</strong>r to verify association between genomic and transcriptomic data of 75 modulatorsconsi<strong>de</strong>ring the number of tumors evaluated, menstrual cycle phase and diagnosis of multipleor solitary tumors. Both genomic and transcriptomic profile were not statistically associatedwith the clustering of samples according to these clinical data (Figure 1A). In addition, thedistribution of the 75 modulators along the chromosomes revealed that 44 of them (58.66%)were mapped in regions not usually <strong>de</strong>scribed as breakpoints targets (1p36.13, 1q41, 2q32.1,2q32.2, 2q35, 4p14, 5q31.2, 7q22.1, 11q13.2, 12p13.31, 14q13.2, 16q22.1, 17q21.31,19q13.32, 19q13.33), and 23 and 5 genes (30.67% and 6.67%, respectively) were mapped intelomeric or pericentromeric regions, which are frequently targets of chromosomal instability(Table 1) (Figure 1B).Gene Set Enrichment Analysis. The results revealed that 32 out of 75 genes wereenriched between 26 modules (Table S4). Among these modules, CORO1A, FGFR1, DDX21and DBN1 genes were the most frequently i<strong>de</strong>ntified whereas DBN1 and FGFR1 showed8

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