This study presents high-resolution analyses of somatic copy-number alterations (SCNAs) in 3131 cancer specimens across 26 histological types. The researchers identified 158 regions of focal SCNA that are significantly altered in multiple cancer types, with 122 regions not explained by known cancer-related genes. These regions include gene families such as the BCL2 family of apoptosis regulators and the NF-κB pathway. The study shows that cancer cells with amplifications of MCL1 and BCL2L1 depend on these genes for survival. A large majority of SCNAs identified in individual cancer types are present in multiple cancer types, suggesting shared biological pathways. The study highlights the prevalence of arm-level SCNAs, which occur more frequently than focal SCNAs. Focal SCNAs are more useful for identifying specific genes targeted by these events. The researchers used the GISTIC algorithm to identify significant focal SCNAs, finding that 158 regions were significantly altered. These regions contain a median of 6.5 genes each, with 25 of the 76 amplification regions containing validated oncogenes. Similarly, 9 of the 82 deletion regions contain validated tumor suppressor genes. The study also found that specific gene families and pathways are over-represented among focal SCNAs, including apoptosis-related genes and the NF-κB pathway. The researchers validated that MCL1 and BCL2L1 are targets of amplifications that encompass them. The study further shows that the majority of significant focal SCNAs in each cancer type are prevalent across other types, indicating shared biological mechanisms. The study provides a comprehensive catalog of SCNAs across multiple cancer types, highlighting the importance of these alterations in cancer development. The findings suggest that many cancer-causing genes are missed due to the limitations of current technologies and that further research is needed to fully understand the role of SCNAs in cancer. The study also emphasizes the importance of functional studies to identify the target genes of these alterations. The results contribute to the understanding of cancer genomics and provide a valuable resource for future research.This study presents high-resolution analyses of somatic copy-number alterations (SCNAs) in 3131 cancer specimens across 26 histological types. The researchers identified 158 regions of focal SCNA that are significantly altered in multiple cancer types, with 122 regions not explained by known cancer-related genes. These regions include gene families such as the BCL2 family of apoptosis regulators and the NF-κB pathway. The study shows that cancer cells with amplifications of MCL1 and BCL2L1 depend on these genes for survival. A large majority of SCNAs identified in individual cancer types are present in multiple cancer types, suggesting shared biological pathways. The study highlights the prevalence of arm-level SCNAs, which occur more frequently than focal SCNAs. Focal SCNAs are more useful for identifying specific genes targeted by these events. The researchers used the GISTIC algorithm to identify significant focal SCNAs, finding that 158 regions were significantly altered. These regions contain a median of 6.5 genes each, with 25 of the 76 amplification regions containing validated oncogenes. Similarly, 9 of the 82 deletion regions contain validated tumor suppressor genes. The study also found that specific gene families and pathways are over-represented among focal SCNAs, including apoptosis-related genes and the NF-κB pathway. The researchers validated that MCL1 and BCL2L1 are targets of amplifications that encompass them. The study further shows that the majority of significant focal SCNAs in each cancer type are prevalent across other types, indicating shared biological mechanisms. The study provides a comprehensive catalog of SCNAs across multiple cancer types, highlighting the importance of these alterations in cancer development. The findings suggest that many cancer-causing genes are missed due to the limitations of current technologies and that further research is needed to fully understand the role of SCNAs in cancer. The study also emphasizes the importance of functional studies to identify the target genes of these alterations. The results contribute to the understanding of cancer genomics and provide a valuable resource for future research.