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It is increasingly clear that cancer as a continuously evolving disease cannot be understood except in the light of evolution.Although massive genomic data for tumor samples are available, our present understanding of cancer evolution is fragmented because clinical samples covering the whole life history of a human tumor from initiation to metastasis have been unavailable.Using a mouse-based xenograft model we conducted a ~2-year experimental evolution of a human cell-derived tumor, and characterized for the first time the complete life history of a tumor at the genomic and transcriptomic levels.We observed interesting patterns, and proposed a cancer devolution model to explain the striking inter-/intra-tumoral genetic heterogeneity in the clinic.