Fig. 3: SV breakpoints in proximity to key genes uniquely contribute to cases of high expression.

a For 1220 cancer cases, copy number versus expression for TERT (left) and MDM2 (right). Cases with SV events upstream of the gene are indicated. b Box plots of expression for TERT, MDM2, ERBB2, and CDK4 by alteration class (“amp.” or gene amplification: 5 or more copies, SV breakpoint within gene body, SV breakpoint 0–20 kb downstream of gene, SV breakpoint 0–20 kb upstream of gene, SV breakpoint 20–50 kb upstream of gene, SV breakpoint 50–100 kb upstream of gene, or none of the above, i.e., “unaligned”). Cases with both SV breakpoint and amplification are assigned here within the amplification group. Asterisks (“*”) denote statistically significant differences versus unaligned group as indicated. c Left: Alterations involving TERT (SV breakpoint 0–50 kb upstream of gene, somatic mutation in promoter, viral integration within TERT promoter, 5 or more gene copies of TERT or MYC) found in the set of 1220 cancers cases having both whole-genome sequencing and RNA data available. Right: Box plot of TERT expression by alteration class. “TERT amp” group does not include cases with other TERT-related alterations (SV, Single Nucleotide Variant or “SNV”, viral). P-values by Mann–Whitney U-test; “*” denotes significant differences versus unaligned group with p < = 0.002, and “**” denotes significant differences with p < 1E−6. n.s., not significant (p > 0.05). Box plots represent 5, 25, 50, 75, and 95%. Points in box plots are colored according to tumor type as indicated in part (c).