DNA amplification is a ubiquitous mechanism of oncogene activation in lung and other cancers.

摘要: Chromosomal translocation is the best-characterized genetic mechanism for oncogene activation. However, there are documented examples of activation by alternate mechanisms, example gene dosage increase, though its prevalence unclear. Here, we answered fundamental question contribution DNA amplification as a molecular driving oncogenesis. Comparing 104 cancer lines representing diverse tissue origins identified genes residing in 'hotspots' and discovered an unexpected frequency activated this mechanism. The 3431 amplicons represent approximately 10 per hematological 36 epithelial genome. Many recurrently amplified oncogenes were previously known to be only disease-specific translocations. 135 hotspots contain 538 unique enriched proliferation, apoptosis linage-dependency genes, reflecting functions advantageous tumor growth. Integrating with expression data validated downstream impact novel events both cell clinical samples. For example, multiple components EGFR-family-signaling pathway, including CDK5, AKT1 SHC1, overexpressed direct result lung cancer. Our findings suggest that far more common than believed specific regions genome amplification.