Fluorescence in situ hybridization (FISH) using break-apart probes is recommended for identifying high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2). Unbalanced MYC break-apart patterns, in which the red or green signal is lost, are commonly reported as an equivocal result by clinical laboratories. In a cohort of 297 HGBCL-DH-BCL2, 13% of tumors had unbalanced MYC break-apart patterns with loss of red (LR; 2%) or loss of green (LG; 11%) signal. To determine the significance of these patterns, MYC rearrangements were characterized by sequencing in 130 HGBCL-DH-BCL2, including 3 LR and 14 LG tumors. A MYC rearrangement was identified for 71% of tumors with LR or LG patterns, with the majority involving immunoglobulin loci or other recurrent MYC rearrangement partners. The architecture of these rearrangements consistently preserved the rearranged MYC allele, with the MYC gene predicted to be on the derivative chromosome containing the signal that is still present in nearly all cases. MYC protein expression, MYC messenger RNA expression, and the proportion of tumors expressing the dark-zone signature was not significantly different between balanced and unbalanced groups. These results support a recommendation that unbalanced MYC break-apart FISH patterns be reported as positive for MYC rearrangement in the context of diagnosing HGBCL-DH-BCL2.

中文翻译：

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不平衡的 MYC 分离 FISH 模式表明 HGBCL-DH-BCL2 中存在 MYC 重排


建议使用分离探针进行荧光原位杂交 （FISH） 以识别具有 MYC 和 BCL2 重排 （HGBCL-DH-BCL2） 的高级别 B 细胞淋巴瘤。不平衡的 MYC 分离模式，其中红色或绿色信号丢失，通常被临床实验室报告为模棱两可的结果。在 297 个 HGBCL-DH-BCL2 的队列中，13% 的肿瘤具有不平衡的 MYC 分离模式，伴有红色信号缺失 （LR; 2%） 或绿色信号缺失 （LG; 11%）。为了确定这些模式的重要性，通过在 130 例 HGBCL-DH-BCL2 中测序来表征 MYC 重排，包括 3 例 LR 和 14 例 LG 肿瘤。71% 的具有 LR 或 LG 模式的肿瘤被发现存在 MYC 重排，其中大多数涉及免疫球蛋白位点或其他复发性 MYC 重排伴侣。这些重排的结构始终保留了重排的 MYC 等位基因，预计 MYC 基因位于衍生染色体上，其中包含在几乎所有情况下仍然存在的信号。平衡组和非平衡组之间 MYC 蛋白表达、MYC 信使 RNA 表达和表达暗区特征的肿瘤比例差异不显著。这些结果支持一项建议，即在诊断 HGBCL-DH-BCL2 的情况下，将不平衡的 MYC 分离 FISH 模式报告为 MYC 重排阳性。