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BMC Bioinformatics. 2023;24(1):62.

ITDetect: a method to detect internal tandem duplication of FMS-like tyrosine kinase (FLT3) from next-generation sequencing data with high sensitivity and clinical application.

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제1저자 이선영, 선충현 · 교신저자 변자민, 윤홍식

소속 (10)
  1. Department of Genomic Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
  2. Center for Precision Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
  3. GenomeOpinion Inc., 117-3 Hoegiro, Dongdaemoon-gu, Seoul, Republic of Korea.
  4. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
  5. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
  6. Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
  7. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. jaminbyun@snu.ac.kr.
  8. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. jaminbyun@snu.ac.kr.
  9. Department of Genomic Medicine, Seoul National University Hospital, Seoul, Republic of Korea. hsyun@snuh.org.
  10. Center for Precision Medicine, Seoul National University Hospital, Seoul, Republic of Korea. hsyun@snuh.org.

Abstract

Internal tandem duplication (ITD) of the FMS-like tyrosine kinase (FLT3) gene is associated with poor clinical outcomes in patients with acute myeloid leukemia. Although recent methods for detecting FLT3-ITD from next-generation sequencing (NGS) data have replaced traditional ITD detection approaches such as conventional PCR or fragment analysis, their use in the clinical field is still limited and requires further information. Here, we introduce ITDetect, an efficient FLT3-ITD detection approach that uses NGS data. Our proposed method allows for more precise detection and provides more detailed information than existing in silico methods. Further, it enables FLT3-ITD detection from exome sequencing or targeted panel sequencing data, thereby improving its clinical application. We validated the performance of ITDetect using NGS-based and experimental ITD detection methods and successfully demonstrated that ITDetect provides the highest concordance with the experimental methods. The program and data underlying this study are available in a public repository.

© 2023. The Author(s).

Keywords

Acute myeloid leukemiaInternal tandem duplicationNext-generation sequencingfragment analysis

Figures

Fig. 1
Fig. 1 A The overall scheme of ITDetect Algorithm. B Correlation between allelic ratio from fragment analysis and allelic ratio from ITDetect. C Integrative genomics viewer (IGV) snapshots of our panel sequencing samples (S05, S07, S19) with multiple FLT3-ITD regions. In the validation process using panel sequencing data, we were able to identify several samples showing unusual patterns. D IGV screenshots of the uncommonly observed FLT3-ITDs

그림 출처: PubMed Central 공개 논문 (PMC9951415)

Conflict of interest statement

The authors declare no conflict of interest.

그 밖의 정보
출판 형태
Journal Article
저널
BMC bioinformatics · eISSN 1471-2105
전자 출판
2023-02-23
MeSH
Humans · Vascular Endothelial Growth Factor Receptor-1* · Protein-Tyrosine Kinases / genetics · Tandem Repeat Sequences / genetics · Leukemia, Myeloid, Acute* / genetics · High-Throughput Nucleotide Sequencing / methods · fms-Like Tyrosine Kinase 3 / genetics · Mutation · Gene Duplication
Substances
Vascular Endothelial Growth Factor Receptor-1 · Protein-Tyrosine Kinases · fms-Like Tyrosine Kinase 3 · FLT3 protein, human
연구비
Ministry of Health & Welfare, Republic of Korea HI14C1277
참고문헌
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