Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch repair deficiency and drug resistance in human leukemia cells

Loss of mismatch repair (MMR) genes is associated with poor cancer prognosis and has been reported to occur through genetic alterations that directly affect the expression of MMR genes such as MSH2. This report identifies a subset of leukemia patients with reduced levels of MSH2 protein but without alterations in the MSH2 gene, and it identifies concurrent deletions in regulators of MSH2 stability as potential contributors to the MSH2 deficiency and associated drug resistance in this and other cancers.