Characteristics and Clinical Value of MYC, BCL2, and BCL6 Rearrangement Detected by Next-generation Sequencing in DLBCL

作者：Yu-Peng Zeng, Ran Wei, Longlong Bao, Tian Xue, Yulan Qin, Min Ren, Qianming Bai, Qianlan Yao, Chengli Yu, Chen Chen, Ping Wei, Baohua Yu, Junning Cao, Xiaoqiu Li, Qunling Zhang, Xiaoyan Zhou · 发表于：The American Journal of Surgical Pathology · 年份：2024 · DOI：10.1097/pas.0000000000002258 · 被引用次数：6 · 研究领域：Lymphoma Diagnosis and Treatment、Chronic Lymphocytic Leukemia Research、CAR-T cell therapy research

MYC , BCL2, and BCL6 rearrangements are clinically important events of diffuse large B-cell lymphoma (DLBCL). The ability and clinical value of targeted next-generation sequencing (NGS) in the detection of these rearrangements in DLBCL have not been fully determined. We performed targeted NGS (481-gene-panel) and break-apart FISH of MYC , BCL2, and BCL6 gene regions in 233 DLBCL cases. We identified 88 rearrangements (16 MYC ; 20 BCL2 ; 52 BCL6 ) using NGS and 96 rearrangements (28 MYC ; 20 BCL2 ; 65 BCL6 ) using FISH. The consistency rates between FISH and targeted NGS for the detection of MYC , BCL2, and BCL6 rearrangements were 93%, 97%, and 89%, respectively. FISH-cryptic rearrangements (NGS+/FISH-) were detected in 7 cases (1 MYC ; 3 BCL2 ; 2 BCL6 ; 1 MYC::BCL6 ), mainly caused by small chromosomal insertions and inversions. NGS-/FISH+ were detected in 38 cases (14 MYC ; 4 BCL2 ; 20 BCL6 ).To clarify the cause of the inconsistencies, we selected 17 from the NGS-/FISH+ rearrangements for further whole genome sequencing (WGS), and all 17 rearrangements were detected with break points by WGS. These break points were all located outside the region covered by the probe of targeted NGS, and most (16/17) were located in the intergenic region. These results indicated that targeted NGS is a powerful clinical diagnostics tool for comprehensive MYC , BCL2, and BCL6 rearrangement detection. Compared to FISH, it has advantages in describing the break point distribution, identifying u...