Despite growing appreciations of the importance of long non-coding RNA (lncRNA) in normal physiology and disease, our knowledge of cancer-related lncRNA remains limited. By repurposing microarray probes, we constructed the expression profile of 10,207 lncRNA genes in approximately 1,300 tumors over four different cancer types. Through integrative analysis of the lncRNA expression profiles with clinical outcome and somatic copy number alteration (SCNA), we identified lncRNA that are associated with cancer subtypes and clinical prognosis, and predicted those that are potential drivers of cancer progression. We validated our predictions by experimentally confirming prostate cancer cell growth dependence on two novel lncRNA. Our analysis provided a resource of clinically relevant lncRNA for development of lncRNA biomarkers and identification of lncRNA therapeutic targets. It also demonstrated the power of integrating publically available genomic datasets and clinical information for discovering disease associated lncRNA.