This study provides a comprehensive analysis of somatic copy-number alterations (SCNAs) in human cancers, focusing on 3,131 cancer specimens from 26 histological types. The authors identified 158 regions of focal SCNA that are significantly altered across multiple cancer types, with 122 of these regions not containing known cancer target genes. Key findings include the enrichment of gene families such as the *BCL2* family of apoptosis regulators and the NF-κB pathway. Functional validation showed that cancer cells harboring amplifications around *MCL1* and *BCL2L1* anti-apoptotic genes depend on their expression for survival. Additionally, the majority of SCNAs identified in individual cancer types are also present in multiple cancer types, highlighting the shared biological pathways underlying cancer development. The study underscores the importance of high-resolution genomic profiling in understanding the genetic landscape of cancer and identifying potential therapeutic targets.This study provides a comprehensive analysis of somatic copy-number alterations (SCNAs) in human cancers, focusing on 3,131 cancer specimens from 26 histological types. The authors identified 158 regions of focal SCNA that are significantly altered across multiple cancer types, with 122 of these regions not containing known cancer target genes. Key findings include the enrichment of gene families such as the *BCL2* family of apoptosis regulators and the NF-κB pathway. Functional validation showed that cancer cells harboring amplifications around *MCL1* and *BCL2L1* anti-apoptotic genes depend on their expression for survival. Additionally, the majority of SCNAs identified in individual cancer types are also present in multiple cancer types, highlighting the shared biological pathways underlying cancer development. The study underscores the importance of high-resolution genomic profiling in understanding the genetic landscape of cancer and identifying potential therapeutic targets.