Frameshift Mutations of the hMSH6 Gene in Human Leukemia Cell Lines

Defects in DNA mismatch repair mechanisms, including frameshift mutations of the hMSH6 and hMSH3 genes at their (C)(8) and (A)(8) tracks, respectively, have been shown to be associated with human malignancies. To clarify the possible involvement of these mutations in hematopoietic malignancies, we screened a total of forty‐four human leukemia and lymphoma cell lines for mutations in the hMSH6 and hMSH3 genes, as well as in other genes required for DNA replication or repair, by polymerase chain reaction single‐strand conformation polymorphism analysis and sequencing analysis. Frameshift mutations at the (C)(8) track of the hMSH6 gene were detected in two cell lines established from lymphoid leukemias. These two cell lines had no wild‐type alleles, and both of them showed microsatellite instability. This is the first report that describes mutations and inactivation of the hMSH6 gene in hematological malignancies, suggesting that defects of the hMSH6 gene may be associated with development of hematological malignancies.