IDENTIFICATION OF A HUMAN TRANSCRIPTION UNIT AFFECTED BY THE VARIANT CHROMOSOMAL TRANSLOCATIONS 2-8 AND 8-22 OF BURKITT-LYMPHOMA

IDENTIFICATION OF A HUMAN TRANSCRIPTION UNIT AFFECTED BY THE VARIANT CHROMOSOMAL TRANSLOCATIONS 2-8 AND 8-22 OF BURKITT-LYMPHOMA
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DOI:
10.1073/pnas.86.9.3257
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发表时间:
1989-05-01
影响因子:
11.1
通讯作者:
BISHOP, JM
BISHOP, JM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SHTIVELMAN, E;HENGLEIN, B;BISHOP, JM

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伯基特淋巴瘤和小鼠浆细胞瘤中的染色体易位通常位于原癌基因MYC内或附近。然而,在某些情况下,这些肿瘤含有变异易位,其断点位于离MYC更远的下游,位于通常称为pvt-1的结构域中。到目前为止,还没有证据表明pvt-1标记了功能基因的位置。在这里,我们报告的一个大的转录单位,包括pvt-1在人类DNA中的识别。我们将这个单位命名为PVT。PVT开始于MYC下游的57个酶对,并占据至少200个酶对的DNA。在伯基特淋巴瘤中发生在MYC下游的一些易位横切PVT;其他易位位于两个基因之间。我们所研究的易位似乎都没有增强PVT的完整等位基因的转录(事实上,它们可能会抑制这种转录),但有些易位与丰富和异常的0.8- 1.0-RNA的产生有关,这些RNA含有PVT的5“外显子和从免疫球蛋白基因恒定区转录的序列(易位的相互参与者)。PVT的鉴定应该有助于探索MYC下游的易位和逆转录病毒DNA在pvt-1附近的插入如何有助于肿瘤发生。
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 translocation 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.