HESI: Emerging spatial genomics and in situ sequencing technologies for carcinogenesis assessment

A defining feature of early carcinogenic processes is the abnormal clonal proliferation of partially transformed cells that have accrued some, but not a complete compendium, of the molecular changes necessary for full malignant transformation. The most primordial of these “preneoplastic” clones are morphologically unrecognizable and their identification instead requires detection of the mutational and epigenetic events that define them. Members of the HESI eSTAR group have recently applied high sensitivity error-corrected DNA sequencing technologies (ecNGS) to detect nascent cancer driver gene mutant (CDM) clones that arise within months after exposure to both established mutagenic and non-mutagenic carcinogens. Although promising, the small size and stochastically-distributed nature of these mutant clones in tissues remains a practical challenge for efficient testing in both clinical and preclinical rodent models. Very recently a new commercial platform has been announced that is able to identify single nucleotide resolution mutations directly in single cells within their native tissue architecture from large (multiple square centimeter) routine FFPE tissue sections. This talk will summarize the multi-omic in situ spatial sequencing technology, review early data and discuss potential applications and pilot studies that could be undertaken by eSTAR in parallel to ongoing ecNGS projects.