The non-steroidal anti-inflammatory
drug sulindac decreases size and number of
adenomas after 4-6 months of treatment for
familial adenomatous polyposis (FAP) patients. However, the underlying mechanism remains unknown. As stem cells are thought to be the
tumor precursor cells, visualizing their behavior is crucial for monitoring
tumor progression. Increased tag diversity in inactive genes is indicative of a protracted clonal evolution and consequently, increased risk for
tumor formation. Therefore, the effect of
sulindac on stem cell dynamics was studied. Normal appearing single crypts were
laser microdissected in placebo- and
sulindac- treated FAP patient tissue after which the methylation patterns were visualized by Next Generation Sequencing. A significant difference in tag diversity over time was found in the
sulindac group compared to the placebo group (*p = 0.018), indicative of a shortened clonal evolution treated
sulindac. The rate of change in tag diversity over time was correlated with
polyp number change over time. No significant difference over time was observed in the percent methylation when comparing placebo vs
sulindac. In conclusion, daily
sulindac administration in FAP patients significantly altered colorectal stem cell dynamics, which might explain the chemopreventive action of this
drug indicating that tag diversity may be used as a predictive
biomarker.