Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma
Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma
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DOI：
10.1038/s41467-019-08578-3
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发表时间：
2019-03-29
影响因子：
16.6
通讯作者：
Rosolowski, Maciej
中科院分区：
文献类型：
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作者：
Lopez, Cristina;Kleinheinz, Kortine;Rosolowski, Maciej
伯基特淋巴瘤（BL）是儿童最常见的B细胞淋巴瘤。在国际癌症基因组联盟（ICGC）中，我们对39例散发性BL进行了全基因组和转录组测序。在这里，我们解开的结构，突变和转录的变化，这有助于MYC癌基因失调连同特异性IG-MYC易位的相互作用。此外，通过绘制IGH易位断裂点，我们提供了证据表明，前体的至少一个子集的BL是一个B细胞准备表达IGHA。我们描述了突变，结构变异和突变过程的景观，并确定了BL发病机制中的一系列驱动基因，这些基因可以通过各种机制靶向，包括IG-非MYC易位，种系和体细胞突变，融合转录本和选择性剪接。
Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.