Kelly Gemma, Bell Andrew, Rickinson Alan
Cancer Research UK Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham, UK.
Nat Med. 2002 Oct;8(10):1098-104. doi: 10.1038/nm758. Epub 2002 Sep 3.
Epstein-Barr virus (EBV) is etiologically linked to endemic Burkitt lymphoma (BL), but its contribution to lymphomagenesis, versus that of the chromosomal translocation leading to c-myc gene deregulation, remains unclear. The virus's growth-transforming (Latency III) program of gene expression is extinguished in tumor cells, and only a single viral protein, the EBV nuclear antigen (EBNA)1, is expressed via the alternative Latency I program. It is not known if BL arises from a B-cell subset in which EBV naturally adopts a Latency I infection or if a clone with limited antigen expression has been selected from an EBV-transformed Latency III progenitor pool. Here we identify a subset of BL tumors in which the Latency III-associated EBNA promoter Wp is active and most EBNAs are expressed, but where a gene deletion has specifically abrogated the expression of EBNA2. This implies that BL can be selected from a Latency III progenitor and that the principal selection pressure is for downregulation of the c-Myc antagonist EBNA2.
爱泼斯坦-巴尔病毒（EBV）在病因学上与地方性伯基特淋巴瘤（BL）相关，但与导致c-myc基因失调的染色体易位相比，其在淋巴瘤发生中的作用仍不清楚。该病毒的生长转化（潜伏III型）基因表达程序在肿瘤细胞中被消除，并且只有一种病毒蛋白，即EBV核抗原（EBNA）1，通过替代的潜伏I型程序表达。尚不清楚BL是否起源于EBV自然采用潜伏I型感染的B细胞亚群，或者是否从EBV转化的潜伏III型祖细胞池中选择了具有有限抗原表达的克隆。在这里，我们鉴定出一部分BL肿瘤，其中与潜伏III型相关的EBNA启动子Wp是活跃的，并且大多数EBNAs都有表达，但基因缺失特异性地消除了EBNA2的表达。这意味着BL可以从潜伏III型祖细胞中选择，并且主要的选择压力是c-Myc拮抗剂EBNA2的下调。
