A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues

Targeted sequencing of 153 genes obtained from clinically annotated post-mortem tissue bulk samples, derived from whole-body donors that are routinely used for educational purposes at human anatomy units. We validated this post-mortem approach using UV-exposed and unexposed epidermal skin tissues and confirm the presence of positively selected NOTCH1/2-, TP53- and FAT1-driven clones. No selection signals were detected in a set of immune genes or housekeeping genes. Additionally, we provide the first evidence for smoking-induced clonal changes in oral epithelia, likely underlying the origin of head and neck carcinogenesis.EGA study EGAS00001006332