Fig. 4

Overexpression of mir-21 in tumors with 3ʹ VMP1 fusion transcripts. Breakpoints and fusion partners for 5ʹ and 3ʹ VMP1 fusion transcripts (a). Gene symbols refer to the corresponding partner gene for each fusion transcript. Red marks in-frame fusions between partner gene coding sequences (CDSs) and blue other fusion transcripts with out-of-frame fusions between partner gene CDSs in bold italic font. Tumors with genomic amplification of the oncogene HER2 (ERBB2) and tumors negative for expression of estrogen receptor (ER) alpha (ESR1) were overrepresented among samples with VMP1 fusion transcripts with p = 0.0018 and p = 0.030, respectively (b). In TCGA data, breast cancer and lung adenocarcinoma were enriched among samples with 3ʹ VMP1 fusions (p = 0.025 and p = 0.0011, respectively); breast cancer also in tumors with 5ʹ VMP1 fusions (p = 0.019, c). Expression of both mature miRNAs from the mir-21 locus, miR-21-5p (d) and miR-21-3p (e), was significantly higher in tumors with 3ʹ VMP1 fusions compared to tumors with no VMP1 fusion transcripts (p = 3.36 × 10⁻⁶ and p = 0.048, respectively). Samples with VMP1 fusions are shown as filled circles for in-frame fusions between partner gene CDSs, open circles with thick line for out-of-frame fusions between partner gene CDSs, and open circles with thin line for all other fusion transcripts. The mRNA expression of PDCD4, an experimentally confirmed target for miR-21-5p, was significantly lower in tumors with 3ʹ VMP1 fusions including mir-21 compared to tumors without mir-21 fusions (p = 0.0019, f). P-values were calculated by Fisher’s exact test for the marginal odds ratios in b, c and by Student’s t-test in d–f