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Relation between microsatellite instability and N-ras mutation and duration of disease free survival in patients with
S Tanosaki1, K Inokuchi, T Shimada
1Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Background:
Microsatellite instability (MIN) appears to be a novel molecular mechanism in carcinogenesis and is believed to reflect multiple replication errors. The authors analyzed MIN in de novo acute leukemia and its association with expression of the human MSH3 (hMSH3) gene and point mutations of the N-ras gene. The relation between MIN and disease free survival also was examined.
Methods:
The authors studied 43 cases of de novo acute leukemia for MIN at 5 loci. They also examined expression of the hMSH3 gene using the reverse transcriptase-polymerase chain reaction method. DNA taken from 36 cases at diagnosis was examined for N-ras mutations. The Kaplan-Meier method was used to estimate patients' disease free survival.
Results:
MIN at 1 locus was found in 7 of the 43 cases (16%) (MIN positive [MIN+] group). There was no correlation between MIN+ and decreased hMSH3 gene expression. Four of the 7 MIN+ cases (57%) had a mutation of the N-ras gene compared with only 1 of the 29 MIN- cases (3%). A correlation between N-ras mutations and MIN was detected (P < 0.003). The MIN+ patients had a shorter disease free survival than the MIN- patients (P < 0.03).
Conclusions:
MIN may be associated with N-ras mutation in some cases of de novo acute leukemia and influence the duration of disease free survival.
Insights
Microsatellite instability (MIN) is linked to N-ras gene mutations in acute leukemia. MIN-positive patients experienced shorter disease-free survival, suggesting MIN impacts leukemia progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Microsatellite instability (MIN) is a molecular mechanism in carcinogenesis, reflecting replication errors.
- MIN is investigated in de novo acute leukemia, exploring its link to hMSH3 gene expression and N-ras mutations.
Purpose of the Study:
- To analyze MIN in de novo acute leukemia.
- To determine the association between MIN, hMSH3 gene expression, and N-ras gene mutations.
- To examine the relationship between MIN and disease-free survival.
Main Methods:
- Studied 43 de novo acute leukemia cases for MIN at 5 loci.
- Assessed hMSH3 gene expression via reverse transcriptase-polymerase chain reaction.
- Analyzed N-ras gene mutations in 36 cases and disease-free survival using Kaplan-Meier method.
Main Results:
- MIN was detected in 16% of cases (7/43).
- No correlation was found between MIN and decreased hMSH3 expression.
- N-ras mutations were significantly higher in MIN-positive cases (57% vs. 3%, P < 0.003).
- MIN-positive patients had significantly shorter disease-free survival (P < 0.03).
Conclusions:
- MIN may be associated with N-ras mutations in de novo acute leukemia.
- MIN appears to influence disease-free survival duration in acute leukemia patients.