CCND2 rearrangements are the most frequent genetic events in cyclin D1- mantle cell lymphoma
CCND2 rearrangements are the most frequent genetic events in cyclin D1- mantle cell lymphoma
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DOI：
10.1182/blood-2012-08-452284
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发表时间：
2013-02-21
期刊：
影响因子：
20.3
通讯作者：
Bea, Silvia
中科院分区：
文献类型：
--
作者：
Salaverria, Itziar;Royo, Cristina;Bea, Silvia
Cyclin D1（-）套细胞淋巴瘤（mcl）尚未被很好地表征，部分原因是它们的识别困难。SOX11最近被确定为MCL的可靠生物标志物，也在细胞周期蛋白D1（-）变体中表达。我们研究了40例MCL形态和免疫表型的淋巴瘤，细胞周期蛋白D1表达/t呈阴性（11;14）（q13;q32），但SOX11呈阳性。这些肿瘤临床表现为全身性淋巴结病、晚期和预后差（5年总生存率为48%）。55%的病例检测到CCND2位点的染色体重排，22例中有18例伴发IG基因，特别是轻链（10个IGK@和5个IGL@）。CCND1、CCND2或CCND3的磷酸化基序未检测到突变。拷贝数阵列分析的32例cyclin D1(-)SOX11(+) MCL患者的整体基因组图谱和高复杂性与传统的cyclin D1(+)/SOX11(+) MCL相似。17p缺失和Ki67高表达使患者的预后明显恶化。对大量cyclin D1(-) MCL患者的综合表征表明，这些肿瘤在临床和生物学上与传统的cyclin D1(+) MCL相似，为这些患者的正确识别和临床管理提供了依据。
Cyclin D1(-) mantle cell lymphomas (MCLs) are not well characterized, in part because of the difficulties in their recognition. SOX11 has been identified recently as a reliable biomarker of MCL that is also expressed in the cyclin D1(-) variant. We investigated 40 lymphomas with MCL morphology and immunophenotype that were negative for cyclin D1 expression/t(11;14)(q13;q32) but positive for SOX11. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and poor outcome (5-year overall survival, 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18 of 22, in particular with light chains (10 IGK@ and 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2, or CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1(-)SOX11(+) MCL patients analyzed by copy number arrays were similar to the conventional cyclin D1(+)/SOX11(+) MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome for the patients. This comprehensive characterization of a large series of cyclin D1(-) MCL patients indicates that these tumors are clinically and biologically similar to the conventional cyclin D1(+) MCL and provides a basis for the proper identification and clinical management of these patients.