Somatic mutations are small DNA errors that accumulate in the genome of ageing cells. They sporadically result in a cellular growth advantage, especially when they occur in cancer-associated genes (e.g., TP53). The sequential accumulation of these driver mutations leads to the formation of malignant tumors. They also underlie micro-clone formation in normal epithelial tissues and emerging evidence suggests spatial competition between these clones and developing tumors, providing new insights in early carcinogenesis. However, spatial competition has not been demonstrated in human tissues yet.

This project hypothesizes that spatial competition directs clonal evolution and carcinogenesis in human epithelial tissues. It aims  to determine spatial interactions between mutant clones and developing tumors using normal and (pre)tumoral tissues sampled from the skin and head- and neck (HN) region in human whole-body donors. We will characterize the clonal landscape using exome sequencing and then map these clonal alterations to their spatial location using spatial transcriptomics and genomic platforms. These spatial maps will then be used to determine spatial interactions between mutant clones and identify different forms of spatial competition.

Results are expected to provide clinically relevant deeper insights in the role of clonal interactions during (early) human carcinogenesis.