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.
套细胞淋巴瘤（MCL）在遗传学上以异常V(D)J重排介导的IG::CCND1易位为特征。CCND1易位及过表达现象亦见于少数具有非典型MCL特征的侵袭性B细胞淋巴瘤中。目前这些肿瘤中产生CCND1重排的机制及其基因组特征尚不明确。本研究通过全基因组/外显子组测序与靶向测序，重建了13例SOX11阴性侵袭性B细胞淋巴瘤的IG::CCND1易位及基因组图谱。易位机制分析显示：3例肿瘤由异常V(D)J重排导致，10例由异常IGH类别转换重组（CSR）或体细胞超突变（SHM）机制介导。其中V(D)J介导易位的肿瘤包括2例母细胞型MCL和1例高级别B细胞淋巴瘤，三者均未出现提示弥漫性大B细胞淋巴瘤（DLBCL）的突变特征。而10例CSR/SHM介导的IGH::CCND1肿瘤主要为大B细胞淋巴瘤，其突变基因常见于DLBCL，其中6例伴有BCL6重排。2例由边缘区淋巴瘤转化的病例携带KLF2、TNFAIP3和KMT2D突变。这些发现拓展了携带CCND1重排的肿瘤谱系，该重排可能作为异常CSR/SHM介导的DLBCL中的继发事件发生，且其突变特征与典型MCL不同。
肿瘤(癌症)患者之家