LOSS OF EXPRESSION OF THE HUMAN MSH3 GENE IN HEMATOLOGICAL MALIGNANCIES

Human MSH3 (hMSH3), previously named human mismatch repair protein 1 ( MRP1), is one of the human homologs of the bacterial DNA mismatch repa ir protein MutS. The hMSH3 gene is expressed at low level in most type s of cells. Using the RT-PCR technique, we examined the expression of the hMSH3 gene in bone marrow cells from 40 patients with various hema tological malignancies. The hMSH3 mRNA was not detectable in 7 cases i ncluding 3 of chronic myelogenous leukemia, 2 of acute myelogenous leu kemia, and 1 of acute lymphocytic leukemia, and 1 of myelodysplastic s yndrome. In addition, 17 cases showed significantly reduced expression of the hMSH3 gene. Southern blot analysis of genomic DNA demonstrated no remarkable changes in the structure and the copy number of the hMS H3 gene in all cases. These results suggest that inactivation of the h MSH3 gene may be involved in the development of hematological malignan cies. (C) 1995 Academic Press, Inc.