Somatic evolution in healthy vs chronically inflamed colon and skin

BMC Seminar Thursday 4th of November, 12:00 in Læknagarður room 201

Speaker: Sigurgeir Ólafsson, PhD student at Cambridge University - Wellcome Sanger Institute

Title: Somatic evolution in healthy vs chronically inflamed colon and skin

Zoom weblink: https://eu01web.zoom.us/j/62692553981

Abstract: Somatic mutations accumulate in all cells of the body as we age. They provide the substrate for Darwinian evolution of cells within the body, with extremely fit cell clones sometimes developing into cancers. This talk will describe somatic evolution of cells within the normal tissue from which cancer develops and the changes to the evolutionary landscape associated with chronic inflammatory diseases of those tissues.

We have performed whole-genome sequencing of hundreds of individual colonic crypts isolated both from normal colon and from the colons of patients suffering from inflammatory bowel disease (IBD). I will describe how IBD is associated with a large increase in the mutation rate of the colon, millimeter scale clonal expansions and positive selection of mutations in immune-related genes in PIGR, IL-17 and TLR pathways.

I will next describe somatic evolution in psoriasis, a second chronic inflammatory disease affecting an epithelial tissue. Although characterized by a marked hyperproliferation of keratinocytes within the epidermis, we have not been able to detect any effect of the disease on the mutation burden or clonal structure of the tissue. Cancer driver mutations are detected in a large fraction of skin cells but their frequency does not seem to differ between lesional and non-lesional skin from psoriasis patients, nor is there evidence of selection of mutations in immune-related genes.