• Whole-genome duplication (WGD) is a pervasive biological phenomenon across prokaryotes, eukaryotes, and somatic tissues, with dual roles in normal development and cancer progression.
• Four principal mechanisms drive WGD: cell fusion, endoreplication, mitotic slippage, and cytokinesis failure, each contributing to polyploidy under different contexts.
• WGD provides genetic redundancy and adaptability in plants and microbes, but in animals, unscheduled WGD promotes chromosomal instability and oncogenesis.
• Recent advances in high-throughput sequencing, multi-omics, and machine learning have revolutionized WGD detection, enabling precise ploidy analysis in cancer research.
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