PMC

A. Boxplots showing MYC activity scores for patients with wild-type (WT) MYC or MYC rearrangements in the Hummel and Sha datasets. Patient with MYC rearrangements in the Hummel dataset were stratified further into non-Ig MYC rearrangements (MYC non-Ig) and Ig MYC rearrangements (MYC Ig). Two-sided Wilcoxon rank test, *: p<0.05, **: p<0.01, ***: p<0.001, ****: p<0.0001. B. AUC curves for Hummel and Sha datasets evaluating the ability of MYC activity scores to predict the presence or absence of MYC rearrangements. C. KM plots for MYC rearrangements, MYC activity scores and MYC activity scores in non-MYC rearranged patients in the Hummel dataset. D. KM plots for MYC rearrangements, MYC activity scores and MYC activity scores in non-MYC rearranged patients in the Sha dataset.

(A) Heat map of reproducible MYC binding peaks observed in CUT&RUN in MCF10A cells expressing WT MYC or MYC S146L. (B) Feature distribution of consensus peaks between WT MYC and MYC S146L. (C) Differential binding analysis of MYC-overlapping H4Ac peaks observed in CUT&RUN in MCF10A cells expressing WT MYC or MYC S146L. (D) Differential binding analysis of MYC-overlapping pS2 peaks observed in CUT&RUN in MCF10A cells expressing WT MYC or MYC S146L.

(A) SA-beta-galactosidase staining on sections of primary lymphoma. MYC inactivation induces SA-beta-galactosidase activity in MYC and MYC p53−/−, but not MYC p19ARF−/− lymphoma. Graph shows quantitation of SA-beta-galactosidase positivity. After MYC inactivation, MYC p19ARF−/− lymphoma had significantly lower SA-beta-galactosidase activity than MYC lymphoma (p = 0.002), while MYC p53−/− lymphoma was not significantly different from MYC lymphoma (p = 0.3). (B) p16INK4A immunohistochemistry on sections of primary lymphoma. MYC inactivation induces an increase in p16INK4A levels in MYC lymphoma, and to a lesser extent, in MYC p53−/− lymphoma, but not in MYC p19ARF−/− lymphoma. Graph shows quantitation of p16INK4A expression. After MYC inactivation, MYC p19ARF−/− lymphoma had significantly lower p16INK4A expression than MYC lymphoma (p = 0.025), while MYC p53−/− lymphoma was not significantly different from MYC lymphoma (p = 0.4). (C) H3K9 trimethylation increased upon MYC inactivation in MYC tumors, but not in MYC p53−/− and MYC p19ARF−/− tumors as measured by Western blot.

A. Summary of potential mechanisms that affect MYC activity. B. Comparison of MYC mRNA expression in samples without and with MYC amplifications in SKCM. Exprs refers to RSEM-normalized gene expression. C. Correlation between the percentage of MYC amplified samples and median aneuploidy scores() across cancer types. D. Enrichment of MYC amplified samples within patients with high MYC scores in independent datasets for lung and breast cancer. E. Classification of four MYC groups using SKCM as example. Samples were ranked by MYC activity scores and colored by MYC amplification status. The percentage of MYC amplifications (17% in SKCM) was used as a cutoff to determine high and low MYC activity scores. F. MYC amplification status in samples with high MYC activity scores. H-Amp and H-NonAmp refer to samples with and without MYC amplifications, respectively, that had high MYC activity scores. Tumor types ordered based on the percentage of MYC amplified samples as indicated behind tumor names.