Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling
Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling
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DOI：
10.1038/35000501
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发表时间：
2000-02-03
期刊：
影响因子：
64.8
通讯作者：
Staudt, LM
中科院分区：
文献类型：
--
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
弥漫性大B细胞淋巴瘤（DLBCL）是非霍奇金淋巴瘤的最常见亚型，在临床上具有异质性：40%的患者对当前治疗反应良好，生存期延长，而其余患者死于该疾病。我们提出，这种变化的自然历史反映了未识别的分子异质性的肿瘤，使用DNA微阵列，我们进行了系统的表征基因表达的B细胞恶性肿瘤。在这里，我们表明，DLBCL患者的肿瘤之间的基因表达的多样性，显然反映了肿瘤的增殖率，宿主反应和分化状态的肿瘤的变化。我们鉴定了两种分子上不同形式的DLBCL，其具有指示B细胞分化的不同阶段的基因表达模式。其中一种表达了生发中心B细胞的特征基因（“类生发中心B型DLBCL”）;第二类表达的基因通常在外周血B细胞的体外活化过程中被诱导（“活化的B样DLBCL”），老年中心B样DLBCL患者的总生存期显著优于活化的B样DLBCL患者，因此，基于基因表达的肿瘤分子分类可以识别以前未检测到的和临床上重要的癌症亚型。
Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours, Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'), Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL, The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.