Cyclin D1-negative mantle cell lymphoma:: a clinicopathologic study based on gene expression profiling
Cyclin D1-negative mantle cell lymphoma:: a clinicopathologic study based on gene expression profiling
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DOI：
10.1182/blood-2005-04-1753
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发表时间：
2005-12-15
期刊：
影响因子：
20.3
通讯作者：
Chan, WC
中科院分区：
文献类型：
--
作者：
Fu, K;Weisenburger, DD;Chan, WC
细胞周期蛋白D1的过度表达被认为是套细胞淋巴瘤（MCL）的发病机制。因此，细胞周期蛋白D1阴性MCL的存在一直是有争议的，难以证实。我们以前的基因表达谱研究确定了几个案件缺乏细胞周期蛋白D1的表达，但有一个典型的MCL的基因表达签名。在此，我们报告了6例细胞周期蛋白D1阴性MCL的临床、病理和遗传学特征。荧光原位杂交（FISH）分析显示6例MCL均具有典型的形态学特征和独特的基因表达特征，但缺乏t（11;14）（q13; q32）。肿瘤细胞也不表达cyclin D1蛋白，但表达cyclin D2（2例）或cyclin D3（4例）。基因表达分析显示cyclin D蛋白表达与相应的mRNA表达水平具有良好的相关性。使用间期FISH，我们没有检测到染色体易位或扩增涉及CCND 2和CCND 3基因座在这些情况下。cyclin D1阴性MCL患者的临床表现与cyclin D1阳性MCL患者相似。总之，细胞周期蛋白D1阴性MCL的病例确实存在，并且是MCL谱的一部分。cyclin D2或D3的上调可能取代cyclin D1参与MCL的发病。
Cyclin D1 overexpression is believed to be essential in the pathogenesis of mantle cell lymphoma (MCL). Hence, the existence of cyclin D1-negative MCL has been controversial and difficult to substantiate. Our previous gene expression profiling study identified several cases that lacked cyclin D1 expression, but had a gene expression signature typical of MCL. Herein, we report the clinical, pathologic, and genetic features of 6 cases of cyclin D1-negative MCL. All 6 cases exhibited the characteristic morphologic features and the unique gene expression signature of MCL but lacked the t(11;14)(q13; q32) by fluorescence in situ hybridization (FISH) analysis. The tumor cells also failed to express cyclin D1 protein, but instead expressed either cyclin D2 (2 cases) or cyclin D3 (4 cases). There was good correlation between cyclin D protein expression and the corresponding mRNA expression levels by gene expression analysis. Using interphase FISH, we did not detect chromosomal translocations or amplifications involving CCND2 and CCND3 loci in these cases. Patients with cyclin D1-negative MCL were similar clinically to those with cyclin D1-positive MCL. In conclusion, cases of cyclin D1-negative MCL do exist and are part of the spectrum of MCL. Up-regulation of cyclin D2 or D3 may substitute for cyclin D1 in the pathogenesis of MCL.