套细胞淋巴瘤 (MCL) 的遗传特征是异常 V(D)J 重排介导的 IG::CCND1 易位。 CCND1 易位和过度表达已在偶尔具有 MCL 异常特征的侵袭性 B 细胞淋巴瘤中发现。这些肿瘤中产生 CCND1 重排的机制及其基因组谱尚不清楚。我们使用全基因组/外显子组和目标测序重建了 IG::CCND1 易位和 13 例 SOX11 阴性侵袭性 B 细胞淋巴瘤的基因组图谱。易位背后的机制是三个肿瘤中的异常 V(D)J 重排以及十个肿瘤中的异常 IGH 类别转换重组 (CSR) 或体细胞超突变 (SHM) 机制。具有 V(D)J 介导的易位的肿瘤是两个母细胞样 MCL 和一个高级别 B 细胞淋巴瘤。他们中没有人具有提示 DLBCL 的突变特征。 CSR/SHM介导的IGH::CCND1的10例肿瘤主要为大B细胞淋巴瘤，其中6例为DLBCL常见突变基因，BCL6重排。2例为边缘区淋巴瘤转化，携带KLF2、TNFAIP3突变。和 KMT2D。这些发现扩大了携带 CCND1 重排的肿瘤谱，这种重排可能作为异常 CSR/SHM 介导的 DLBCL 的继发事件而发生，并与不同于 MCL 的突变谱相关。© 2024。作者。

Mantle cell lymphoma (MCL) is genetically characterized by the IG::CCND1 translocation mediated by an aberrant V(D)J rearrangement. CCND1 translocations and overexpression have been identified in occasional aggressive B-cell lymphomas with unusual features for MCL. The mechanism generating CCND1 rearrangements in these tumors and their genomic profile are not known. We have reconstructed the IG::CCND1 translocations and the genomic profile of 13 SOX11-negative aggressive B-cell lymphomas using whole genome/exome and target sequencing. The mechanism behind the translocation was an aberrant V(D)J rearrangement in three tumors and by an anomalous IGH class-switch recombination (CSR) or somatic hypermutation (SHM) mechanism in ten. The tumors with a V(D)J-mediated translocation were two blastoid MCL and one high-grade B-cell lymphoma. None of them had a mutational profile suggestive of DLBCL. The ten tumors with CSR/SHM-mediated IGH::CCND1 were mainly large B-cell lymphomas, with mutated genes commonly seen in DLBCL and BCL6 rearrangements in 6. Two cases, which transformed from marginal zone lymphomas, carried mutations in KLF2, TNFAIP3 and KMT2D. These findings expand the spectrum of tumors carrying CCND1 rearrangement that may occur as a secondary event in DLBCL mediated by aberrant CSR/SHM and associated with a mutational profile different from that of MCL.© 2024. The Author(s).