Deciphering the cellular origin and evolution that underlie the initial phases of cancer formation is crucial for efficient early screening and intervention. Precancerous stages often span several years, remaining occult, thus complicating the identification of early tumor initiation events.
In our study, we harnessed a base editor-based lineage tracing technique, SMALT, to systematically map the origin and evolution of intestinal precancers in mouse models at single-cell resolution.
Through integrated analyses of single-cell phylogenies and comprehensive genome sequencing, we significantly improved our understanding of the complexities in the precancerous stages of colorectal cancer.
Cancer genomic sequencing typically unveils a single founding clone in a malignant tumor, but we found that premalignant adenomas can have polyclonal origins with multiple distinct lineages expanding concurrently.
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