Fig. 1.

YAP1 fusion proteins are predominantly localized in the nucleus of ST-EPN-YAP1s. a Unsupervised 2D representation of sample correlations based on DNA methylation data by t-distributed stochastic neighbor embedding (t-SNE) dimensionality reduction. Individual samples (n = 137) are color-coded in the respective class color for ST-EPN-RELA (red) and ST-EPN-YAP1 (cyan). Representative samples further analyzed in this study are indicated by triangles. b YAP1 fusion types at protein level. Red dashed lines indicate fusion sites. Proteins are drawn to scale. TID TEA domain-containing factor-interaction domain for TEAD binding, WW protein–protein interaction domain, TAD transcriptional activation domain for TEAD, MAML mastermind-like domain, Ser serine-rich region, Pro proline-rich region. c Graphical summary of the ST-EPN-YAP1 cohort (n = 45) analyzed in this study, classified according to Genome-wide DNA methylation profiles. RNA sequencing data were available for seven samples. Absolute numbers of fusion partners are indicated. Color codes are identical to b. d–f Representative micrographs show d haematoxylin and eosin staining (H&E), immunostaining for e YAP1 and f phosphorylated YAP1 (S127) (p-YAP1) for human ST-EPN-YAP1 tumors (scale bar, 50 µm). g, h Detection of g YAP1-MAMLD1 (140 kDa) or h YAP1-FAM118B (120 kDa) fusions with YAP1 wild-type (WT) (75 kDa) in ST-EPN-YAP1 (YAP1#1-4) and ST-EPN-RELA tumors (RELA#1-2) by western blotting of cytosolic and nuclear fractions with an antibody recognizing the C-terminus of YAP1 protein. Actin and LaminB1 were used as an internal control for cytoplasmic and nuclear fractions. i Quantification of protein levels in human primary ST-EPNs. The values were normalized to the respective internal controls. j Detection of phosphorylated YAP1-MAMLD1 (140 kDa) in the nucleus of human ST-EPN-YAP1 tumors. Of note, phosphorylated YAP1 protein was not detected in the cytoplasm nor the nucleus in human ST-EPN-RELA tumors