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Blood. 1997 Mar 1;89(5):1740-7.

Mutations and loss of expression of a mismatch repair gene, hMLH1, in leukemia and lymphoma cell lines.

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  • 1Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.

Abstract

Defects in genes involved in DNA mismatch repair have been detected in both hereditary and sporadic tumors of colon, endometrium, and ovary and suggested to be associated with tumorigenesis. To investigate disruptions of the mismatch repair system in hematological malignancies, we examined alterations of the human mutL homologue 1 (hMLH1) gene, a member of the mismatch repair gene family, in a total of 43 human leukemia and lymphoma cell lines, by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing analyses. Mutations of the hMLH1 gene were detected in three cell lines established from lymphoid leukemias. Moreover, Northern and Western blot analyses showed that expression of hMLH1 transcript or protein was abrogated in these three leukemia cell lines. Further studies for microsatellite loci showed that these cell lines without hMLH1 expression showed microsatellite instability. This is the first report that describes mutations and inactivation of the hMLH1 gene in human leukemia cells, suggesting that disruption of DNA mismatch repair system may play an important role in the development of human lymphoid leukemias.

PMID:
9057658
[PubMed - indexed for MEDLINE]
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