Fig. 5: Integration of DNA and RNA findings for variant annotation.

a Top panel shows absolute copy number on the y axis and the structural variants (SVs) that result in PAX3-FOXO3 fusion in patient H134768. Lower panel displays RNA fusion product created by the corresponding genomic SVs. b tSNE clustering of methylation data from rhabdomyosarcoma samples color-coded by disease subtype (ARMS: alveolar, ERMS: embryonal, SCRMS: spindle cell, and SRMS: sclerosing). The patient harboring the PAX3-FOXO3 fusion clusters with the ARMS samples. c Top panel shows the chromoplexy event among chromosomes 6, 9, and 18, resulting in the localization of NFIB enhancer to the MYB locus in patient H133676. Lower panel displays H3K27me3 chromatin marks from Drier et al., Nature Genetics 2016. d Boxplot shows the MYB expression in transcripts per million (TPM) across the cohort. Center line indicates the median and whiskers extend within +/−1.5x the interquartile range (IQR) from the box. The patient with MYB-NFIB event (H133676) is highlighted in orange, demonstrating that the SV event in panels c associates with overexpression of MYB, validating the SV as an enhancer-hijacking event. e Diagram of SV events targeting TP53 gene body in osteosarcoma patients (n = 12, the 13th patient’s event breakpoints fall outside of the gene body). SVs are shown as arrows with absolute copy number on the y axis (gray dots) overlaid over the exonic structure of TP53 (TRA: translocation, DUP: duplication, DEL: deletion, INV: inversion). f Boxplot shows the comparison of TP53 expression in RNA between TP53-rearranged samples and those without any rearrangement with a center line indicating the median and whiskers extending within +/−1.5 x the IQR (two-sided Mann–Whitney U test, p = 1.645e-03). Raw data for panel a–c can be accessed at the dbGAP study. Source data for panel e are provided in Supplementary Data 9. Source data for panels d, f are provided at the data repository.