Table S1. TCGA samples included in study. Table S2. Gene weights of MYC signatures. Table S3. Pre-ranked Gene Set Enrichment Analysis results of cancer type-specific MYC activity signatures. Table S4. MYC AUC characteristics. Table S5. Recurrent MYC mutations. Table S6. Multivariate Cox regression model assessing the relationship between patient prognosis and MYC activity scores, immune infiltration and expression of E2F family members in SKCM. Table S7. Prognostic results of individual datasets from GEO and PRECOG. Table S8. GEO and PRECOG datasets.
ARTICLE ABSTRACTc-MYC (MYC) is deregulated in more than 50% of all cancers. While MYC amplification is the most common MYC-deregulating event, many other alterations can increase MYC activity. We thus systematically investigated MYC pathway activity across different tumor types. Using a logistic regression framework, we established tumor type–specific, transcriptomic-based MYC activity scores that can accurately capture MYC activity. We show that MYC activity scores reflect a variety of MYC-regulating mechanisms, including MYCL and/or MYCN amplification, MYC promoter methylation, MYC mRNA expression, lncRNA PVT1 expression, MYC mutations, and viral integrations near the MYC locus. Our MYC activity score incorporates all of these mechanisms, resulting in better prognostic predictions compared with MYC amplification status, MYC promoter methylation, and MYC mRNA expression in several cancer types. In addition, we show that tumor proliferation and immune evasion are likely contributors to this reduction in survival. Finally, we developed a MYC activity signature for liquid tumors in which MYC translocation is commonly observed, suggesting that our approach can be applied to different types of genomic alterations. In conclusion, we developed a MYC activity score that captures MYC pathway activity and is clinically relevant.
By using cancer type–specific MYC activity profiles, we were able to assess MYC activity across many more tumor types than previously investigated. The range of different MYC-related alterations captured by our MYC activity score can be used to facilitate the application of future MYC inhibitors and aid physicians to preselect patients for targeted therapy.