Cell-of-Origin in Diffuse Large B-Cell Lymphoma: Are the Assays Ready for the Clinic?
Cell-of-Origin in Diffuse Large B-Cell Lymphoma: Are the Assays Ready for the Clinic?
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DOI：
10.14694/edbook_am.2015.35.e458
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发表时间：
2015-01-01
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影响因子：
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通讯作者：
Scott, David W
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文献类型：
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作者：
Scott, David W
弥漫性大B细胞淋巴瘤（DLBCL）是全球最常见的淋巴瘤，由一组异质性癌症组成，这些癌症根据共同的形态学、免疫表型和侵袭性临床行为分类在一起。现在认识到，这种恶性肿瘤包括至少两个不同的分子亚型确定的基因表达谱：激活B细胞样（ABC）和生发中心B细胞样（GCB）组-细胞的起源（COO）分类。这两组有不同的基因突变景观，病理生物学和治疗后的结果。越来越多的证据表明，新型药物在一个或另一个COO组中具有选择性活性，使COO成为预测性生物标志物。因此，现在迫切需要准确和强大的方法来分配COO，以支持临床试验，并最终指导患者的治疗决策。COO的“金标准”方法是基于使用微阵列技术对来自新鲜冷冻组织的RNA进行基因表达谱分析（GEP），当福尔马林固定石蜡包埋组织（FFPET）活检是标准诊断材料时，这是一种不切实际的解决方案。这篇综述概述了COO分类的历史，然后研究适用于FFPET活检的COO检测的实际实施。免疫组化（IHC）为基础的算法和基因表达为基础的测定法，适用于高度降解的RNA从FFPET进行了讨论。最后，技术和实际的挑战，仍然需要解决之前，强大的基因表达为基础的检测方法用于DLBCL患者的常规管理概述。
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma worldwide and consists of a heterogeneous group of cancers classified together on the basis of shared morphology, immunophenotype, and aggressive clinical behavior. It is now recognized that this malignancy comprises at least two distinct molecular subtypes identified by gene expression profiling: the activated B-cell-like (ABC) and the germinal center B-cell-like (GCB) groups-the cell-of-origin (COO) classification. These two groups have different genetic mutation landscapes, pathobiology, and outcomes following treatment. Evidence is accumulating that novel agents have selective activity in one or the other COO group, making COO a predictive biomarker. Thus, there is now a pressing need for accurate and robust methods to assign COO, to support clinical trials, and ultimately guide treatment decisions for patients. The "gold standard" methods for COO are based on gene expression profiling (GEP) of RNA from fresh frozen tissue using microarray technology, which is an impractical solution when formalin-fixed paraffin-embedded tissue (FFPET) biopsies are the standard diagnostic material. This review outlines the history of the COO classification before examining the practical implementation of COO assays applicable to FFPET biopsies. The immunohistochemistry (IHC)-based algorithms and gene expression-based assays suitable for the highly degraded RNA from FFPET are discussed. Finally, the technical and practical challenges that still need to be addressed are outlined before robust gene expression-based assays are used in the routine management of patients with DLBCL.