Faculty of Biological Sciences, University of Leeds, Leeds, UK.
Haematological Malignancy Diagnostic Service, St James' University Hospital, Leeds, UK.
Br J Haematol. 2021 Feb;192(3):599-604. doi: 10.1111/bjh.17246. Epub 2020 Nov 29.
Cell-of-origin subclassification of diffuse large B cell lymphoma (DLBCL) into activated B cell-like (ABC), germinal centre B cell-like (GCB) and unclassified (UNC) or type III by gene expression profiling is recommended in the latest update of the World Health Organization's classification of lymphoid neoplasms. There is, however, no accepted gold standard method or dataset for this classification. Here, we compare classification results using gene expression data for 68 formalin-fixed paraffin-embedded DLBCL samples measured on four different gene expression platforms (Illumina wG-DASL arrays, Affymetrix PrimeView arrays, Illumina TrueSeq RNA sequencing and the HTG EdgeSeq DLBCL Cell of Origin Assay EU using an established platform agnostic classification algorithm (DAC) and the classifier native to the HTG platform, which is CE marked for in vitro diagnostic use (CE-IVD). Classification methods and platforms show a high level of concordance, with agreement in at least 80% of cases and rising to much higher levels for classifications of high confidence. Our results demonstrate that cell-of-origin classification by gene expression profiling on different platforms is robust, and that the use of the confidence value alongside the classification result is important in clinical applications.
在世界卫生组织最新修订的淋巴肿瘤分类中,弥漫性大 B 细胞淋巴瘤(DLBCL)可通过基因表达谱分为活化 B 细胞样(ABC)、生发中心 B 细胞样(GCB)和未分类(UNC)或 III 型。然而,目前还没有被广泛认可的金标准方法或数据集来进行这种分类。在这里,我们比较了 68 例福尔马林固定石蜡包埋的 DLBCL 样本的基因表达数据,这些样本分别在四个不同的基因表达平台(Illumina wG-DASL 阵列、Affymetrix PrimeView 阵列、Illumina TrueSeq RNA 测序和 HTG EdgeSeq DLBCL Cell of Origin Assay EU)上进行了测量,使用了一种已建立的平台独立分类算法(DAC)和 HTG 平台的本地分类器(该分类器已获得体外诊断使用的 CE 标志(CE-IVD))。分类方法和平台显示出高度的一致性,至少有 80%的病例达成一致,对于高置信度的分类,一致性水平更高。我们的结果表明,不同平台上基于基因表达谱的细胞起源分类是稳健的,在临床应用中,使用分类结果的置信值非常重要。