文章：

在骨髓瘤患者中，8q24的易位将MYC与含有超增强子的基因并置，导致过表达和预后不良

Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients

原文发布日期：2014-03-14

DOI: 10.1038/bcj.2014.13

类型: Original Article

开放获取: 是

英文摘要：

Secondary MYC translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including IGH, IGK and IGL, which juxtapose the immunoglobulin (Ig) enhancers next to MYC in 8/23 samples. The remaining samples had partner loci including XBP1, FAM46C, CCND1 and KRAS, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of MYC in these samples. Patients with MYC translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near MYC result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of MYC and an aggressive disease phenotype.

摘要翻译： 

骨髓瘤中的继发性MYC易位已被证明在疾病的发生和发展中具有重要作用。本研究采用DNA捕获和大规模并行测序方法，对104例初诊骨髓瘤样本中的配对染色体进行了鉴定。在21例（20%）样本中发现了8q24断点，其配对位点包括IGH、IGK和IGL，其中8/23例样本中免疫球蛋白（Ig）增强子与8号染色体上的MYC基因并列。其余样本的配对位点包括XBP1、FAM46C、CCND1和KRAS，这些基因在B细胞成熟或骨髓瘤发病机制中具有重要作用。对断点周围区域的分析表明，配对染色体上存在超级增强子，基因表达分析显示这些样本中MYC表达增加。携带MYC易位的患者无进展生存期和总生存期均缩短。我们推测，MYC附近的易位断点导致该基因与来自特定基因座的超级增强子共定位，这些基因座对发生易位的细胞类型的发育至关重要。在骨髓瘤中，这些基因座包括Ig基因座以及对浆细胞发育和骨髓瘤发病机制重要的基因座，从而导致MYC表达增加并呈现侵袭性疾病表型。

原文链接：

Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients