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Updated: Feb 23, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Cost-effective screening of DNMT3A coding sequence identifies somatic mutation in pediatric T-cell acute
Bronisława Szarzyńska-Zawadzka1, Maria Kosmalska1, Łukasz Sędek2
1Institute of Human Genetics Polish Academy of Sciences, Poznań, Poland.
Background And Objectives:
In pediatric T-cell acute lymphoblastic leukemia (T-ALL), risk assignment schemes preclude reliable prediction of outcome, and thus, new prognostic factors are needed. Mutations in DNMT3A are candidate prognostic and classification markers in adults with acute myeloid leukemia (AML) and T-ALL and thus were considered as candidates prognostic markers in pediatric T-ALL.
Patients And Methods:
DNMT3A mutational status was investigated in 74 pediatric T-ALL samples collected at diagnosis. We applied high-resolution melt (HRM) analysis and Sanger sequencing to study the hotspot position (R882) within catalytic MTase domain and exons coding for other functional domains of the protein, known to be mutated in the wide spectrum of hematological malignancies.
Results:
We demonstrate a low frequency of mutations in DNMT3A coding sequence in pediatric T-ALL (1.4%, n = 1/74). We identified missense mutation, p.Ala644Thr, which has not been described previously in pediatric T-ALL, but is recurrent in adults with T-ALL and AML.
Conclusions:
Low frequency of DNMT3A mutations in pediatric T-ALL is in striking contrast to adult T-ALL and renders the necessity for the search of other candidate prognostic markers. Combined Sanger sequencing-HRM approach offers a cost-effective option for genotyping DNMT3A coding sequence, with potential clinical application in other hematological malignancies.
