Poulsen Christian Bjørn, Borup Rehannah, Nielsen Finn Cilius, Borregaard Niels, Hansen Mads, Grønbaek Kirsten, Møller Michael Boe, Ralfkiaer Elisabeth
Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Denmark.
Eur J Haematol. 2005 Jun;74(6):453-65. doi: 10.1111/j.1600-0609.2005.00429.x.
Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation on the Affymetrix HG-U133A oligonucleotide arrays and improve the classification, we determined the expression profiles of pretreatment, diagnostic samples from 52 primary nodal DLBCL.
First, three previously published gene lists were converted to the HG-U133A probe sets and used for hierarchical clustering. In this way, three subtypes, including the GCB type (n = 20), the ABC type (n = 25) and an intermediate group, Type-3 (n = 5), were distinguished. The CD10 and Bcl-6 expression as well as t(14;18) translocation were prevalent, but not exclusive to the GCB type. By contrast, MUM1 was only expressed in the ABC and in Type-3 samples. The 5-year survival was similar between the groups, but GCB patients showed a better initial response to CHOP or CHOP-like regimens than the remaining patients and tended to have less advanced disease and lower IPI scores. As a next step, an improved set of classifier genes was generated by analysis of 34 patients that were consistently classified as GCB or ABC in the above analyses. Seventy-eight genes were selected and demonstrated on two previously published data sets (Shipp et al. Nat Med 2002;8:68-74 and Houldsworth et al. Blood 2004;103:1862-1868) to exhibit a higher specificity than the original gene lists.
We conclude that gene expression profiling with Affymetrix Genechips is efficient to distinguish between GCB and ABC types of DLBCL and that these are likely to represent separate biological entities. The Genechip platform is highly standardised and therefore useful for future prospective investigations to establish the value of gene expression profiling in the clinical management of DLBCL.
基于基因表达特征的弥漫性大B细胞淋巴瘤（DLBCL）分层聚类先前已被用于将DLBCL分为生发中心B细胞（GCB）型和活化B细胞（ABC）型。为了检验在Affymetrix HG-U133A寡核苷酸阵列上进行跨平台验证并改进分类是否可行，我们确定了52例原发性淋巴结DLBCL预处理诊断样本的表达谱。
首先，将三个先前发表的基因列表转换为HG-U133A探针集并用于分层聚类。通过这种方式，区分出三种亚型，包括GCB型（n = 20）、ABC型（n = 25）和一个中间组，即3型（n = 5）。CD10和Bcl-6表达以及t(14;18)易位很常见，但并非GCB型所特有。相比之下，MUM1仅在ABC型和3型样本中表达。各组之间的5年生存率相似，但GCB患者对CHOP或类似CHOP方案的初始反应优于其余患者，且疾病进展往往较少，国际预后指数（IPI）评分较低。下一步，通过对上述分析中一直被分类为GCB或ABC的34例患者进行分析，生成了一组改进的分类基因。选择了78个基因，并在两个先前发表的数据集（Shipp等人，《自然医学》2002年；8：68 - 74以及Houldsworth等人，《血液》2004年；103：1862 - 1868）上进行展示，结果表明这些基因比原始基因列表具有更高的特异性。
我们得出结论，使用Affymetrix基因芯片进行基因表达谱分析能够有效区分DLBCL的GCB型和ABC型，并且它们可能代表不同的生物学实体。基因芯片平台高度标准化，因此对于未来前瞻性研究确定基因表达谱分析在DLBCL临床管理中的价值很有用。
