Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Cell. 2011 Sep 30;147(1):95-106. doi: 10.1016/j.cell.2011.07.048.
Chromosomal rearrangements, including translocations, require formation and joining of DNA double strand breaks (DSBs). These events disrupt the integrity of the genome and are frequently involved in producing leukemias, lymphomas and sarcomas. Despite the importance of these events, current understanding of their genesis is limited. To examine the origins of chromosomal rearrangements we developed Translocation Capture Sequencing (TC-Seq), a method to document chromosomal rearrangements genome-wide, in primary cells. We examined over 180,000 rearrangements obtained from 400 million B lymphocytes, revealing that proximity between DSBs, transcriptional activity and chromosome territories are key determinants of genome rearrangement. Specifically, rearrangements tend to occur in cis and to transcribed genes. Finally, we find that activation-induced cytidine deaminase (AID) induces the rearrangement of many genes found as translocation partners in mature B cell lymphoma.
染色体易位等染色体重排需要形成并连接 DNA 双链断裂（DSB）。这些事件会破坏基因组的完整性，并且经常与白血病、淋巴瘤和肉瘤的发生有关。尽管这些事件非常重要，但目前对其起源的了解还很有限。为了研究染色体易位的起源，我们开发了易位捕获测序（TC-Seq）技术，该技术可以在原代细胞中全面记录染色体易位。我们检测了来自 4 亿个 B 淋巴细胞的超过 18 万个易位，结果表明 DSB 之间的邻近性、转录活性和染色体区室是基因组重排的关键决定因素。具体来说，易位倾向于发生在顺式和转录基因上。最后，我们发现激活诱导胞嘧啶脱氨酶（AID）诱导许多成熟 B 细胞淋巴瘤中转录因子易位伙伴基因的重排。
