Shtivelman E, Henglein B, Groitl P, Lipp M, Bishop J M
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Proc Natl Acad Sci U S A. 1989 May;86(9):3257-60. doi: 10.1073/pnas.86.9.3257.
Chromosomal translocations in Burkitt lymphoma and mouse plasmacytomas typically lie within or near the protooncogene MYC. In some instances, however, these tumors contain variant translocations with breakpoints located more distant from and downstream of MYC, in a domain commonly known as pvt-1. Until now, there has been no evidence that pvt-1 marks the location of a functional gene. Here we report the identification of a large transcriptional unit in human DNA that includes pvt-1. We have designated this unit as PVT. PVT begins 57 kilobase pairs downstream of MYC and occupies a minimum of 200 kilobase pairs of DNA. Some of the translocations that occur downstream of MYC in Burkitt lymphoma transect PVT; others lie between the two genes. None of the translocations we have studied appear to enhance transcription from an intact allele of PVT (indeed, they may inactivate that transcription), but some are associated with the production of abundant and anomalous 0.8- to 1.0-kilobase RNAs that contain the 5' exon of PVT and sequences transcribed from the constant region of an immunoglobulin gene (the reciprocal participant in the translocation). Identification of PVT should facilitate the exploration of how translocations downstream of MYC and insertions of retroviral DNA in the vicinity of pvt-1 might contribute to tumorigenesis.
伯基特淋巴瘤和小鼠浆细胞瘤中的染色体易位通常发生在原癌基因MYC内部或其附近。然而，在某些情况下，这些肿瘤含有变异易位，其断点位于距离MYC更远且在MYC下游的一个区域，该区域通常称为pvt - 1。到目前为止，尚无证据表明pvt - 1标记了一个功能基因的位置。在此我们报告在人类DNA中鉴定出一个包含pvt - 1的大型转录单位。我们将这个单位命名为PVT。PVT在MYC下游57千碱基对处起始，占据至少200千碱基对的DNA。伯基特淋巴瘤中发生在MYC下游的一些易位会切断PVT；其他易位则位于这两个基因之间。我们研究的所有易位似乎都不会增强PVT完整等位基因的转录（实际上，它们可能会使该转录失活），但有些易位与产生大量异常的0.8至1.0千碱基RNA有关，这些RNA包含PVT的5'外显子以及从免疫球蛋白基因恒定区转录的序列（易位中的另一个参与部分）。PVT的鉴定应有助于探索MYC下游的易位以及pvt - 1附近逆转录病毒DNA的插入如何可能导致肿瘤发生。
