Fig. 5.

The UVSSA gene in ML017 and ML017/ET xenografts. The genomic sequence of the UVSSA gene harboured CNA (heterozygous loss) in the ML017/ET tumours only (a). The genomic alterations (CNV and SNV) were orthogonally validated by ddPCR (b). Each orange bar indicates the copy number of the UVSSA gene (reference y-axis on the right); blue lines indicate the fractional abundance of SNV (reference y-axis on the left) calculated as reported in the Material and methods section. The presence of the SNV and the CNA was evaluated in tumour biopsies from ML017-bearing mice after different cycles of exposure to trabectedin (ML017 ind res): the heterozygous loss is detectable after 21 drug doses while the fractional abundance of the SNV increased after 18 drug doses. mRNA and protein levels of the UVSSA gene were analysed: in panel c, bar graphs show transcriptional expression levels of UVSSA in ML017 and ML017/ET untreated samples. Data show the absence of UVSSA in ML017/ET (orange) untreated samples compared to ML017 (green). These differences were also highlighted by western blot analysis (d)