Department of Pathology, Johns Hopkins University, School of Medicine, 600 North Wolfe Street, Carnegie 401, Baltimore, MD 21205, USA.
Mob DNA. 2013 Oct 17;4(1):22. doi: 10.1186/1759-8753-4-22.
Hematolymphoid neoplasms frequently harbor recurrent genetic abnormalities. Some of the most well recognized lesions are chromosomal translocations, and many of these are known to play pivotal roles in pathogenesis. In lymphoid malignancies, some translocations result from erroneous V(D)J-type events. However, other translocation junctions appear randomly positioned and their underlying mechanisms are not understood.
We tested the hypothesis that genomic repeats, including both simple tandem and interspersed repeats, are involved in chromosomal translocations arising in hematopoietic malignancies. Using a database of translocation junctions and RepeatMasker annotations of the reference genome assembly, we measured the proximity of translocation sites to their nearest repeat. We examined 1,174 translocation breakpoints from 10 classifications of hematolymphoid neoplasms. We measured significance using Student's t-test, and we determined a false discovery rate using a random permutation statistics technique.
Most translocations showed no propensity to involve genomic repeats. However, translocation junctions at the transcription factor 3 (TCF3)/E2A immunoglobulin enhancer binding factors E12/E47 (E2A) locus clustered within, or in proximity to, transposable element sequences. Nearly half of reported TCF3 translocations involve a MER20 DNA transposon. Based on this observation, we propose this sequence is important for the oncogenesis of TCF3-PBX1 acute lymphoblastic leukemia.
血液淋巴肿瘤常存在反复出现的遗传异常。其中一些最知名的病变是染色体易位，许多易位在发病机制中起着关键作用。在淋巴恶性肿瘤中，一些易位是由于错误的 V(D)J 型事件引起的。然而，其他易位的连接点似乎是随机定位的，其潜在机制尚不清楚。
我们检验了这样一个假设，即基因组重复序列，包括简单串联重复序列和散在重复序列，参与了造血恶性肿瘤中发生的染色体易位。我们使用易位连接点数据库和参考基因组组装的 RepeatMasker 注释，测量了易位位点与其最近重复序列的接近程度。我们研究了来自 10 种血液淋巴肿瘤分类的 1174 个易位断点。我们使用学生 t 检验测量显著性，并使用随机排列统计技术确定错误发现率。
大多数易位没有倾向于涉及基因组重复序列。然而，转录因子 3（TCF3）/E2A 免疫球蛋白增强子结合因子 E12/E47（E2A）基因座的易位连接点聚集在转座元件序列内或附近。近一半报道的 TCF3 易位涉及 MER20 DNA 转座子。基于这一观察结果，我们提出该序列对 TCF3-PBX1 急性淋巴细胞白血病的发生具有重要意义。
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