A pan‐cancer atlas of cancer hallmark‐associated candidate driver lnc RNA s

Substantial cancer genome sequencing efforts have discovered many important driver genes contributing to tumorigenesis. However, very little is known about the genetic alterations of long non‐coding RNA s (lnc RNA s) in cancer. Thus, there is a need for systematic surveys of driver lnc RNA s. Through integrative analysis of 5918 tumors across 11 cancer types, we revealed that lnc RNA s have undergone dramatic genomic alterations, many of which are mutually exclusive with well‐known cancer genes. Using the hypothesis of functional redundancy of mutual exclusivity, we developed a computational framework to identify driver lnc RNA s associated with different cancer hallmarks. Applying it to pan‐cancer data, we identified 378 candidate driver lnc RNA s whose genomic features highly resemble the known cancer driver genes (e.g. high conservation and early replication). We further validated the candidate driver lnc RNA s involved in ‘Tissue Invasion and Metastasis’ in lung adenocarcinoma and breast cancer, and also highlighted their potential roles in improving clinical outcomes. In summary, we have generated a comprehensive landscape of cancer candidate driver lnc RNA s that could act as a starting point for future functional explorations, as well as the identification of biomarkers and lnc RNA ‐based target therapy.