Distribution of mutations in DNMT3A gene and the suitability of mutations in R882 codon for MRD monitoring in patients with AML
Language English Country Japan Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26290145
DOI
10.1007/s12185-015-1856-3
PII: 10.1007/s12185-015-1856-3
Knihovny.cz E-resources
- Keywords
- AML preleukemic stem cells, DNMT3A gene mutations, MRD, Next-generation sequencing,
- MeSH
- Leukemia, Myeloid, Acute genetics MeSH
- DNA Methyltransferase 3A MeSH
- DNA (Cytosine-5-)-Methyltransferases genetics MeSH
- Adult MeSH
- Codon genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Mutation, Missense * MeSH
- Monitoring, Physiologic * MeSH
- Biomarkers, Tumor genetics MeSH
- Neoplasm Proteins genetics MeSH
- Neoplasm, Residual MeSH
- Aged MeSH
- Amino Acid Substitution MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA Methyltransferase 3A MeSH
- DNA (Cytosine-5-)-Methyltransferases MeSH
- DNMT3A protein, human MeSH Browser
- Codon MeSH
- Biomarkers, Tumor MeSH
- Neoplasm Proteins MeSH
The DNA methyl-transferase 3A gene (DNMT3A) is the third most frequently mutated gene in cytogenetically normal acute myeloid leukemia (CN-AML) patients (20-30 %), who belong to a group of patients with intermediate risk. About 60 % of mutations in this gene have been identified in the arginine codon R882. To date, there is no consensus on whether these mutations can be used as biomarkers for monitoring of minimal residual disease and management of preemptive AML therapy. We studied the occurrence of mutations in the DNMT3A gene in our cohort of patients and their persistence during AML treatment. Using next-generation sequencing, we identified four mutations in 11/25 of our analyzed patients--frequent R882C and R882H mutations, rare Y735S mutation, and a novel L347P mutation. Mutation R882C was detected in 5/11, R882H in 4/11 patients, and Y735S and L347P in one patient each. In 4/7 patients initially carrying mutations in the R882 codon, we found the persistence of mutations also during complete remission with, however, no correlation to AML kinetics. Our findings suggest that mutations in the DNMT3A gene can only be used as a biomarker for those AML patients in whom DNMT3A mutation is lost after therapy.
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