Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada.
Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada.
Blood. 2024 Oct 10;144(15):1611-1616. doi: 10.1182/blood.2024025603.
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.
荧光原位杂交（FISH）使用分离探针，推荐用于识别具有 MYC 和 BCL2 重排的高级别 B 细胞淋巴瘤（HGBCL-DH-BCL2）。临床实验室通常将不平衡的 MYC 分离模式（红色或绿色信号丢失）报告为不确定结果。在 297 例 HGBCL-DH-BCL2 队列中，13%的肿瘤具有不平衡的 MYC 分离模式，表现为红色（LR；2%）或绿色（LG；11%）信号丢失。为了确定这些模式的意义，对 130 例 HGBCL-DH-BCL2 中的 MYC 重排进行了测序，包括 3 例 LR 和 14 例 LG 肿瘤。LR 或 LG 模式的肿瘤中 71%鉴定出 MYC 重排，大多数涉及免疫球蛋白基因座或其他常见的 MYC 重排伙伴。这些重排的结构始终保留了重排的 MYC 等位基因，MYC 基因预测位于含有信号的衍生染色体上，在几乎所有情况下，该信号仍然存在。平衡和不平衡组之间 MYC 蛋白表达、MYC 信使 RNA 表达和表达暗区特征的肿瘤比例没有显著差异。这些结果支持在诊断 HGBCL-DH-BCL2 时，将不平衡的 MYC 分离 FISH 模式报告为 MYC 重排阳性的建议。
