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 repair protein MutS. The hMSH3 gene is expressed at low level in most types of cells. Using the RT-PCR technique, we examined the expression of the hMSH3 gene in bone marrow cells from 40 patients with various hematological malignancies. The hMSH3 mRNA was not detectable in 7 cases including 3 of chronic myelogenous leukemia, 2 of acute myelogenous leukemia, and 1 of acute lymphocytic leukemia, and 1 of myelodysplastic syndrome. 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 hMSH3 gene in all cases. These results suggest that inactivation of the hMSH3 gene may be involved in the development of hematological malignancies.
Inokuchi
K
K
Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan.
Ikejima
M
M
Watanabe
A
A
Nakajima
E
E
Orimo
H
H
Nomura
T
T
Shimada
T
T
D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009101:Multiple Myeloma / Q000235:genetics; D000074081:MutS Homolog 3 Protein; D009190:Myelodysplastic Syndromes / Q000235:genetics; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D011506:Proteins; D013762:Tetrahydrofolate Dehydrogenase; C078444:MSH3 protein, human; C421109:multidrug resistance-associated protein 1