Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing
Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing
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DOI：
10.1038/ng.2469
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发表时间：
2012-12-01
期刊：
影响因子：
30.8
通讯作者：
Siebert, Reiner
中科院分区：
文献类型：
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作者：
Richter, Julia;Schlesner, Matthias;Siebert, Reiner
Burkitt淋巴瘤是一种成熟的侵袭性B细胞淋巴瘤，起源于生发中心B细胞(1)。它的细胞遗传学特征是Burkitt易位t(8；14)(q24；q32)及其变异体，它将MYC癌基因与三个免疫球蛋白基因中的一个并列(2)。因此，MYC被解除管制，导致基因表达的巨大扰动(3)。然而，MYC放松管制本身似乎不足以推动Burkitt淋巴增生症。通过对4例免疫球蛋白基因(IG)-MYC易位的典型Burkitt淋巴瘤的全基因组、全外显子组和转录组测序，我们确定了7个重复突变的基因。其中一个基因ID3被定位于Burkitt淋巴瘤的局部纯合缺失区域(4)。在扩大的队列中，53例分子定义的Burkitt淋巴瘤中有36例(68%)携带潜在的破坏性ID3突变。这些都在体细胞超突变模体上得到了极大的丰富。在其他47例带有IG-MYC易位的B细胞淋巴瘤中，只有6例(13%)携带ID3突变。这些发现表明ID3失活和IG-MYC易位之间的协同作用是Burkitt淋巴肿大的一个标志。
Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells(1). Its cytogenetic hallmark is the Burkitt translocation t(8;14)(q24;q32) and its variants, which juxtapose the MYC oncogene with one of the three immunoglobulin loci(2). Consequently, MYC is deregulated, resulting in massive perturbation of gene expression(3). Nevertheless, MYC deregulation alone seems not to be sufficient to drive Burkitt lymphomagenesis. By whole-genome, whole-exome and transcriptome sequencing of four prototypical Burkitt lymphomas with immunoglobulin gene (IG)-MYC translocation, we identified seven recurrently mutated genes. One of these genes, ID3, mapped to a region of focal homozygous loss in Burkitt lymphoma(4). In an extended cohort, 36 of 53 molecularly defined Burkitt lymphomas (68%) carried potentially damaging mutations of ID3. These were strongly enriched at somatic hypermutation motifs. Only 6 of 47 other B-cell lymphomas with the IG-MYC translocation (13%) carried ID3 mutations. These findings suggest that cooperation between ID3 inactivation and IG-MYC translocation is a hallmark of Burkitt lymphomagenesis.