Aggressive B-cell lymphomas are currently classified based in part upon the presence or absence of translocations involving BCL2, BCL6, and MYC. Most clinical laboratories employ fluorescence in situ hybridization (FISH) analysis for the detection of these rearrangements. The potential role of RNA-based sequencing approaches in the evaluation of malignant lymphoma is currently unclear. In this study, we performed RNA sequencing (RNAseq) in 37 cases of aggressive B-cell lymphomas using a commercially available next generation sequencing assay and compared results to previously performed FISH studies. RNAseq detected 1/7 MYC (14%), 3/8 BCL2 (38%) and 4/8 BCL6 (50%) translocations identified by FISH. RNAseq also detected 1 MYC/IGH fusion in a case not initially tested by FISH due to low MYC protein expression and 2 BCL6 translocations that were not detected by FISH. RNAseq identified the partner gene in each detected rearrangement, including a novel EIF4G1-BCL6 rearrangement. In summary, RNAseq complements FISH for the detection of rearrangements of BCL2, BCL6 and MYC in the evaluation and classification of aggressive B-cell lymphomas by detecting rearrangements that may be cryptic by FISH methods and by identifying the rearrangement partner genes. Detection of these clinically important translocations may be optimized by combined use of FISH and RNAseq.

目前，对侵略性B细胞淋巴瘤的分类部分基于是否存在涉及BCL2，BCL6和MYC的易位。大多数临床实验室采用荧光原位杂交（FISH）分析来检测这些重排。目前尚不清楚基于RNA的测序方法在评估恶性淋巴瘤中的潜在作用。在这项研究中，我们使用市售的下一代测序测定法对37例侵袭性B细胞淋巴瘤病例进行了RNA测序（RNAseq），并将结果与​​先前进行的FISH研究进行了比较。RNAseq检测到1/7 MYC（14％），3/8 BCL2（38％）和4/8 BCL6FISH鉴定出（50％）易位。由于MYC蛋白表达低和FISH未检测到2个BCL6易位，因此RNAseq在最初未通过FISH检测的情况下还检测到1个MYC / IGH融合。RNAseq在每个检测到的重排中都鉴定了伴侣基因，包括新的EIF4G1-BCL6重排。总而言之，RNAseq通过检测FISH方法可能是隐性的重排并鉴定重排伴侣基因，补充了FISH，以检测BCL2，BCL6和MYC在侵袭性B细胞淋巴瘤的评估和分类中的重排。这些临床上重要的易位的检测可以通过结合使用FISH和RNAseq进行优化。