Related Experiment Video
Updated: Mar 7, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Detection the Frequency and Characteristics of FLT3 Internal Tandem Duplication Mutations by Capillary
Background:
FLT3-internal tandem duplication mutations (ITDs) are found in approximately 30% of patients with acute myeloid leukemia (AML) and are markers of poor prognosis. However, the characteristics of FLT3/ ITDs in Chinese AML patients have rarely been reported. The aim of this study was to analyze the frequency and characteristics of FLT3/ITDs in Chinese AML patients.
Methods:
In the selected 152 cases of Chinese AML patients, capillary electrophoresis (CE) was used to analyze the frequency and characteristics of FLT3/ITDs. Next-generation sequencing was used to analyze the sequences of FLT3/ITDs positive patients. The differences of clinical features between FLT3/ITD positive group and FLT3/ITD negative group were estimated by statistical analysis.
Results:
42 cases (27.6%) were FLT3/ITDs-positive, in which 34 cases (81%) had a single duplication, and the remaining 8 cases (19%) had 2 or more ITDs. Median ITD size was 42 bp and median ITD allelic ratio was 0.25. Using next-generation sequencing, ITDs integrating in non-juxtamembrane (JM) domains were detected in 12 ITDs (24%) and in JM domains were detected in 38 ITDs (76%). Furthermore, duplication of at least one residue between Y591 and Y599 was detected in 48 (96%) of all 50 ITDs, and the insertion site was strongly correlated with ITD size: more C-terminal located inserted fragments were significantly longer.
Conclusions:
Our data provide further evidence of the heterogeneity of FLT3/ITDs among different subgroups in Chinese AML patients. ITDs varied widely, but hotspots were concentrated. These results also suggest that nextgeneration sequencing is a useful method for detection of FLT3/ITDs sequences.
Insights
FLT3-internal tandem duplication (ITD) mutations are common in Chinese acute myeloid leukemia (AML) patients, showing significant heterogeneity in size and location. Next-generation sequencing is effective for characterizing these poor-prognosis markers.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations are prevalent in acute myeloid leukemia (AML), associated with unfavorable prognosis.
- Limited data exists on the specific characteristics of FLT3-ITD in Chinese AML populations.
Purpose of the Study:
- To investigate the frequency and molecular characteristics of FLT3-ITD mutations in Chinese AML patients.
- To analyze the correlation between FLT3-ITD features and clinical parameters.
Main Methods:
- Capillary electrophoresis (CE) was employed to screen 152 Chinese AML patients for FLT3-ITD.
- Next-generation sequencing (NGS) was utilized for detailed sequence analysis of FLT3-ITD positive cases.
- Statistical analysis compared clinical features between FLT3-ITD positive and negative groups.
Main Results:
- FLT3-ITD mutations were identified in 27.6% (42/152) of patients, with a median size of 42 bp and allelic ratio of 0.25.
- Most mutations (81%) were single duplications; 76% involved juxtamembrane (JM) domains, and 96% affected residues Y591-Y599.
- Insertion site correlated with ITD size, with C-terminal insertions being longer.
Conclusions:
- FLT3-ITD mutations exhibit significant heterogeneity in Chinese AML patients, though mutation hotspots are concentrated.
- NGS is a valuable tool for comprehensive FLT3-ITD sequence analysis.
- Understanding these genetic variations can inform prognostic assessments and therapeutic strategies.
