Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13728-32. doi: 10.1073/pnas.1202882109. Epub 2012 Aug 6.
Many tumors are characterized by recurrent translocations between a tissue-specific gene and a proto-oncogene. The juxtaposition of the Ig heavy chain gene and Myc in Burkitt's lymphoma and in murine plasmacytoma is a classic example. Regulatory elements within the heavy chain constant region locus are required for Myc translocation and/or deregulation. However, many genes are regulated by cis-acting elements at distances up to 1,000 kb outside the locus. Such putative distal elements have not been examined for the heavy chain locus, particularly in the context of Myc translocations. We demonstrate that a transgene containing the Ig heavy chain constant region locus, inserted into five different chromosomal locations, can undergo translocations involving Myc. Furthermore, these translocations are able to generate plasmacytomas in each transgenic line. We conclude that the heavy chain constant region locus itself includes all of the elements necessary for both the translocation and the deregulation of the proto-oncogene.
许多肿瘤的特征是组织特异性基因与原癌基因之间的反复易位。伯基特淋巴瘤和鼠浆细胞瘤中免疫球蛋白重链基因和 Myc 的并置就是一个经典的例子。重链恒定区基因座内的调节元件是 Myc 易位和/或失调控所必需的。然而，许多基因受到距离基因座 1000kb 以外的顺式作用元件的调节。在重链基因座中，特别是在 Myc 易位的情况下，尚未对这些假定的远端元件进行检查。我们证明，包含免疫球蛋白重链恒定区基因座的转基因，插入到五个不同的染色体位置，可以发生涉及 Myc 的易位。此外，这些易位能够在每个转基因系中产生浆细胞瘤。我们的结论是，重链恒定区基因座本身包含了所有必需的元素，用于原癌基因的易位和失调控。
