Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma
Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma
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DOI：
10.3324/haematol.2013.091827
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发表时间：
2014-04-01
期刊：
影响因子：
10.1
通讯作者：
Siebert, Reiner
中科院分区：
文献类型：
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作者：
Aukema, Sietse M.;Kreuz, Markus;Siebert, Reiner
影响MYC癌基因的染色体易位是伯基特淋巴瘤的生物学标志，但也发生在其他成熟B细胞淋巴瘤的子集中。如果伴有靶向BCL 2和/或BCL 6癌基因的染色体断裂，则这些MYC易位阳性（MYC+）淋巴瘤被称为双重打击淋巴瘤，否则应用术语单一打击淋巴瘤。为了表征这些MYC+淋巴瘤而不是伯基特淋巴瘤的生物学特征，我们在排除了通过基因表达谱定义的分子伯基特淋巴瘤之后，探索了80个MYC易位阳性淋巴瘤（31个单发、46个双发和3个BCL 6状态未知的MYC+淋巴瘤）的分子、病理和临床方面。单次打击和双次打击淋巴瘤的比较显示，MYC伴侣（IG/非IG），基因组复杂性，MYC表达或基因表达谱没有差异。双重打击淋巴瘤更频繁地显示出生殖中心B细胞样基因表达谱，并具有较高的IGH和MYC突变频率。基因表达谱分析显示BCL 6（+）/MYC+和BCL 2（+）/MYC+双重打击淋巴瘤之间有130个差异表达基因。BCL 2（+）/MYC+双重打击淋巴瘤更常表现为生发中心B样基因表达谱。根据MYC伴侣（IG/非IG）对所有淋巴瘤的分析显示无实质性差异。在这一系列淋巴瘤中，仅在少数病例中给予免疫化疗，与分子伯基特淋巴瘤和无MYC断裂的淋巴瘤的结局相比，单次打击和双次打击淋巴瘤的结局相似。我们的数据表明，在排除分子伯基特淋巴瘤和儿科病例后，MYC+淋巴瘤在生物学上是相当同质的，具有单次打击和双重打击淋巴瘤以及IG-MYC和非IG-MYC+淋巴瘤共享各种分子特征。
Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC+) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC+ lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC+-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC+ and BCL2(+)/MYC+ double-hit lymphomas. BCL2(+)/MYC+ double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC+ lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC+ lymphomas sharing various molecular characteristics.