Abstract 341: Co-detection of BCR::ABL1 common and atypical fusion and mutation using a novel NGS assay, Dup-Seq BCR-ABL1

Abstract

Abstract The clinical management of CML and Ph+ ALL patients requires the identification of BCR::ABL1 transcript variants and drug resistance mutations. Currently these assessments need to be performed using separate assays resulting in higher sample requirements, longer turnaround times and higher costs. In this study a custom NGS assay (Dup-Seq BCR-ABL1) was developed and validated that enables co-detection and identification of transcript variants (common and atypical) and resistance mutations. The assay design covers BCR exon 1 to ABL1 exon 10 and employs duplicate PCR amplification of BCR-ABL1 from a single source of the 1st strand cDNA initiated by ABL1 specific priming. The custom data analysis pipeline enables overlapped mutation calling from duplicates as well as transcript determination. The assay minimizes the low-level artifacts that can be seen with other NGS-based BCR::ABL1 assays. This study demonstrates that the Dup-Seq BCR-ABL1 assay achieves high accuracy (PPA for fusion: 0.985; PPA and NPA for mutation at 0.978 and 0.9999, respectively) and sensitivity (LoD for mutation detection at 3% from 10,000 copies of BCR-ABL1 input). The use of the Dup-Seq BCR-ABL1 assay for both transcript variant identification and mutation detection provides comprehensive and accurate results for the clinical management of CML and Ph+ ALL patients while reducing sample requirements, testing costs and turnaround time. Citation Format: Jin Li, Zhenyu Yan, Lin Shi, Wei Li, Weihua Liu, Cynthia Spittle, Chad Galderisi. Co-detection of BCR::ABL1 common and atypical fusion and mutation using a novel NGS assay, Dup-Seq BCR-ABL1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 341.