Tissue profiling technologies present opportunities for understanding transition from precancerous lesions to malignancy, which may impact risk stratification, prevention, and even cancer treatment. A human precancer atlas (PCA) building effort is ongoing to tackle the significant challenge of decoding the heterogeneity among cells, specimens, and patients. Here, we discuss the findings resulting from atlases built across precancer types, including those found in colon, breast, lung, stomach, cervix, and skin, using bulk, single-cell, and spatial profiling strategies. We highlight two main themes that emerge across precancer types: the ordering of molecular events that occur during tumor progression and the fluctuation of microenvironmental response during precancer progression. We further highlight the key challenges of data integration across large cohorts of patients, and the need for computational tools to reliably annotate and quality control high-volume, high-dimensional data.

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