Illuminating the noncoding genome in cancer.

Understanding the mechanisms underlying tumorigenesis requires comprehensive annotation of the cancer genome. The majority of the human genome consists of noncoding regions, harboring functional elements that regulate the expression of protein-coding genes, including proto-oncogenes or tumor-suppressor genes. Technologies such as whole-genome and long-read sequencing provide powerful means to identify alterations in the noncoding genome of cancer cells, paving the way for the study of their functional relevance. Recent analyses of noncoding alterations have revealed additional mechanisms underlying tumor development, progression and response to therapies, and uncovered new targets for drug development. Here we highlight recent findings about noncoding alterations, review established and emerging methods and models to study these alterations, and discuss the outlook for noncoding alterations as therapeutic targets.