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 uncharacterized partners, and detecting FISH-cryptic rearrangements. However, the lack of high-sensitivity caused by insufficient probe coverage is the main limitation of the current technology.

中文翻译：

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新一代测序检测 DLBCL 中 MYC、BCL2 和 BCL6 重排的特征和临床价值。


MYC、BCL2 和 BCL6 重排是弥漫性大 B 细胞淋巴瘤 (DLBCL) 的临床重要事件。靶向下一代测序 (NGS) 在检测 DLBCL 中这些重排方面的能力和临床价值尚未完全确定。我们对 233 例 DLBCL 病例进行了靶向 NGS（481 基因组）和 MYC、BCL2 和 BCL6 基因区域的分离 FISH。我们使用NGS鉴定了88个重排（16个MYC；20个BCL2；52个BCL6），使用FISH鉴定了96个重排（28个MYC；20个BCL2；65个BCL6）。 FISH 与靶向 NGS 检测 MYC、BCL2 和 BCL6 重排的一致性率分别为 93%、97% 和 89%。在 7 例病例中检测到 FISH 隐性重排 (NGS+/FISH-)（1 例 MYC；3 例 BCL2；2 例 BCL6；1 例 MYC::BCL6），主要由小染色体插入和倒位引起。在38例中检测到NGS-/FISH+（14例MYC；4例BCL2；20例BCL6）。为了澄清不一致的原因，我们从NGS-/FISH+重排中选择了17例进行进一步的全基因组测序（WGS），所有17例均被检测到。通过全基因组测序（WGS）检测到断点重排。这些断点均位于目标NGS探针覆盖的区域之外，并且大多数（16/17）位于基因间区域。这些结果表明，靶向 NGS 是一种强大的临床诊断工具，可用于全面检测 MYC、BCL2 和 BCL6 重排。与 FISH 相比，它在描述断点分布、识别未表征的伙伴以及检测 FISH 神秘重排方面具有优势。然而，由于探头覆盖范围不足而导致缺乏高灵敏度是当前技术的主要限制。