Analysis of Aurora-A and hMPS1 mitotic kinases in mantle cell lymphoma
Analysis of Aurora-A and hMPS1 mitotic kinases in mantle cell lymphoma
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DOI：
10.1002/ijc.21370
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发表时间：
2006-01-15
影响因子：
6.4
通讯作者：
Hernández, L
中科院分区：
文献类型：
--
作者：
Camacho, E;Beà, S;Hernández, L
Aurora-A和hMPS 1是参与纺锤体检查点和中心体复制调节的激酶，其改变与不同肿瘤模型中的细胞转化和染色体不稳定性相关。在这项研究中，我们已经检查了这些基因在58套细胞淋巴瘤（MCL）和4个MCL相关细胞系的可能改变。Aurora-A还在46例弥漫性大B细胞淋巴瘤（DLBCL）中进行了检查。Aukora-A和hMPS 1 mRNA表达水平与肿瘤增殖活性相关。有趣的是，具有最高数量或染色体不平衡的MCL病例也显示极高的Aurora-A mRNA表达值。在任何肿瘤或细胞系中均未检测到Aurora-A基因扩增，而在23%的MCL和4种细胞系中的3种中观察到半合子hMPS 1基因缺失。然而，在这些病例中未检测到表达改变或基因突变。Aurora-A提出的癌症易感性多态性变体（P31 I）在MCL、DLBCL、慢性淋巴细胞白血病和431名健康对照中观察到相似的频率。然而，3例MCL和4例DLBCL具有这种多态性的纯合变体，具有特殊的临床特征，在MCL中具有不寻常的早期表现和第二上皮恶性肿瘤，在DLBCL中具有结节起源。这些发现表明，Aurora-A和hMPS 1畸变是罕见的侵袭性淋巴瘤，但Aurora-A过度表达可能有助于偶尔MCL的染色体数目的改变。尽管Aurora-A P31 I多态性变异体并不直接参与这些淋巴瘤的遗传易感性，但它可能调节这些肿瘤的临床表现。(c)2005 Wiley-Liss，Inc.
Aurora-A and hMPS1 are kinases involved in spindle checkpoint and centrosome duplication regulation and whose alterations have been associated with cell transformation and chromosome instability in different tumor models. In this study, we have examined the possible alterations of these genes in 58 mantle cell lymphomas (MCLs) and 4 MCL-related cell lines. Aurora-A was also examined in 46 diffuse large B-cell lymphomas (DLBCLs). Aukora-A and hMPS1 mRNA expression levels were related to tumor proliferative activity. Interestingly, a MCL case with the highest number or chromosomal imbalances also showed an extremely high value of Aurora-A mRNA expression. No Aurora-A gene amplifications were detected in any tumor or cell line, whereas hemizygous hMPS1 gene deletions were observed in 23% of MCLs and 3 of the 4 cell lines. However, no expression alterations or gene mutations were detected in these cases. The Aurora-A proposed cancer susceptibility polymorphic variant (P31I) was observed with a similar frequency in MCL, DLBCL, chronic lymphocytic leukemia and in the 431 healthy controls. However, the 3 MCLs and 4 DLBCLs with the homozygous variant of this polymorphism had particular clinical characteristics with an unusual early-age presentation and second epithelial malignancies in MCL and extranodal origin in DLBCL. These findings indicate that Aurora-A and hMPS1 aberrations are uncommon in aggressive lymphomas but Aurora-A overexpression may contribute to numerical chromosomal alterations in occasional MCL. Although the Aurora-A P31I polymorphic variant is not directly involved in a genetic predisposition to these lymphomas, it may modulate the clinical presentation of these tumors. (c) 2005 Wiley-Liss, Inc.