Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Annu Rev Pathol. 2013 Jan 24;8:79-103. doi: 10.1146/annurev-pathol-020712-164004. Epub 2012 Sep 4.
Studies of B cell lymphomas in the early 1980s led to the cloning of genes (c-MYC and IGH) at a chromosome translocation breakpoint. A rush followed to identify recurrently translocated genes in all types of cancer, which led to remarkable advances in our understanding of cancer genetics. B lymphocyte tumors commonly bear chromosome translocations to immunoglobulin genes, which points to a role for antibody gene diversification processes in tumorigenesis. The discovery of activation-induced cytidine deaminase (AID) and the use of murine models to study translocation have led to a new understanding of how these events contribute to the genesis of lymphomas. Here, we review these advances with a focus on AID and insights gained from the study of translocations in primary cells.
20 世纪 80 年代早期对 B 细胞淋巴瘤的研究导致了染色体易位断裂点处基因(c-MYC 和 IGH)的克隆。随后,人们急于鉴定所有类型癌症中经常易位的基因,这使得我们对癌症遗传学的认识取得了显著进展。B 淋巴细胞肿瘤通常带有免疫球蛋白基因的染色体易位,这表明抗体基因多样化过程在肿瘤发生中起作用。激活诱导的胞嘧啶脱氨酶(AID)的发现以及使用小鼠模型研究易位,使我们对这些事件如何促成淋巴瘤的发生有了新的认识。在这里,我们重点关注 AID,并从对原代细胞易位的研究中获得了一些见解。