Abstract
Numerous cancer drivers have been identified, but they are specific to a given cancer type and condition; universal cancer drivers and universal cancer mechanisms still remain largely unclear. Here, we identified the deadliest universal drivers for all cancers via developing algorithms to analyze massive RNAseqs and clinical data from The Cancer Genome Atlas (TCGA). In general, noncoding RNAs primarily serve as the most important inducers and suppressors for all types of cancers. In particular, pseudogenes are primary inducers, and specifically the antisense RNA RP11-335K5.2 serves as the most universal cancerous driver, independently of the cancer type and condition. Therefore, noncoding RNAs, instead of proteins as conventionally thought, primarily drive cancer, which establishes a novel field for future cancer research and therapy.