MSH3 deficiency initiates EMAST without protumorigenic transformation of human colon epithelial cells

Introduction: Elevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature in certain cases of sporadic colorectal cancer and has been linked to MSH3-deficiency. It is currently unclear whether EMAST carries protumorigenic properties in humans, specifically as cancer development in MSH3-deficient mice is not enhanced. However, a mutator phenotype is different between species as the genetic positions of repetitive sequences are not conserved. Here we studied the molecular effects of human MSH3-deficiency. Methods: HCT116 and HCT116+chr3 (both MSH3-deficient) and primary h…