Sack, L. M. et al. Cell 173, 499–514 (2018).
Some genes can lead to cancer when mutated, whereas others drive cancer as a result of copy-number increases. Sack et al. generated a library of almost 30,000 barcoded human open reading frames to screen for genes that either stimulate or suppress proliferation when overexpressed. Their lentiviral screening vectors allowed for inducible expression and tagging, as well as quantitative detection. The researchers carried out screens in mammary, fibroblast and pancreatic cell lines, and found that around 10% of genes regulate proliferation, often in a highly tissue-specific manner. Candidate genes from the screen were enriched for known oncogenes and tumor-suppressor genes, and tissue-specific drivers were typically associated with the tumor tissue of origin. Many of the candidate genes are not commonly mutated in cancers but are associated with tissue-specific focal somatic copy-number alterations.