Improved Sensitivity in Detection of FMS-like Tyrosine Kinase Internal Tandem Duplication of a Method Using Next-Generation Sequencing Data

• Published in: Blood 2016-12, Vol.128 (22), p.2844-2844
• Main Authors: Shin, Junghoon, Kim, Daeyoon, Hong, Yoojin, Koh, Youngil, Yun, Hongseok, Shin, Dong-Yeop, Yoon, Sung-Soo, Kim, Inho, Lee, Junglim, Kim, Byung-Su
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.2844.2844

We developed new ITD detection algorithm (ITDetect) based on whole exome sequencing (WES) data for FMS-like tyrosine kinase internal tandem duplication (FLT3-ITD). ITDetect is based on BWA and is specified for ITD detection including FLT3-ITD. We validated and compared result of ITDetect with other ITD detecting algorithms using nested polymerase chain reaction (PCR) method. Nested PCR uses two types of primer specified for FLT3-ITD detection. In 81 acute myeloid leukemia patients with WES data, FLT3-ITD was positive in 11 patients (13%) when called with ITDetect, all of whom were validated with nested PCR. Meanwhile FLT3-ITD was positive only in 7/81 patients by conventional PCR. The concordance rate of ITDetect and nested PCR was 95% (77/81). ITDetect showed better ITD detection performance when compared with previously reported ITD callers. In large AML cohort (n=213), patients who were positive for FLT3-ITD with nested-PCR but not with conventional PCR had shorter survival outcomes than patients who were negative for FLT3-ITD with nested PCR, suggesting clinical significance of sensitive FLT3-ITD detection. In conclusion, we developed more sensitive detection methods for FLT3-ITD based on WES data that is clinically meaningful. Utilization of more sensitive detection method than conventional PCR in clinic should be considered. [Display omitted] [Display omitted] [Display omitted] No relevant conflicts of interest to declare.