Knecht H, Bachmann E, Brousset P, Rothenberger S, Einsele H, Lestou V S, Delsol G, Bachmann F, Ambros P F, Odermatt B F
Department of Internal Medicine, CHUV University Hospital, Lausanne, Switzerland.
Oncogene. 1995 Feb 2;10(3):523-8.
We have recently identified in Epstein-Barr virus (EBV) positive Hodgkin's disease (HD) a variant of the latent membrane protein 1 (LMP1) oncogene characterized by four point mutations and a 30 base pair deletion. These findings led us to test whether such mutants were also present in other lymphoproliferative disorders (LPD). We analysed 98 EBV DNA positive cases (67 LPD, 15 benign conditions, 16 lymphoblastoid cell lines) by PCR for deletions within the LMP1 gene. DNA sequencing of the region coding for the carboxy terminal protein domain was performed on 24 cases. In 13 cases the same combination of 4 point mutations at positions 168,320, 168,308, 168,295 and 168,225 was identified. Of these cases, 12 had an additional point mutation at position 168,357 and eight at position 168,355, and nine had a 30 base pair deletion including nucleotides 168,285 to 168,256. These deletion mutants were identified in HD, angioimmunoblastic lymphadenopathy, B-immunoblastic lymphoma, peripheral T-cell lymphoma, and two lymphoblastoid cell lines. Our findings reveal a high frequency of non-random point mutations at preferential sites within the 3' (carboxy terminal) region of the LMP1 oncogene. The association of these mutational hot spots with LPD suggests that they are involved in EBV related lymphomagenesis and that they define a clinically relevant EBV strain.
我们最近在爱泼斯坦-巴尔病毒（EBV）阳性的霍奇金淋巴瘤（HD）中鉴定出一种潜伏膜蛋白1（LMP1）癌基因变体，其特征为四处点突变和一段30个碱基对的缺失。这些发现促使我们去检测此类突变体是否也存在于其他淋巴增殖性疾病（LPD）中。我们通过聚合酶链反应（PCR）分析了98例EBV DNA阳性病例（67例LPD、15例良性病症、16株淋巴母细胞系），以检测LMP1基因内的缺失情况。对24例病例进行了编码羧基末端蛋白结构域区域的DNA测序。在13例病例中鉴定出了位于168,320、168,308、168,295和168,225位点的相同四处点突变组合。在这些病例中，12例在168,357位点还有一处额外的点突变，8例在168,355位点有额外点突变，9例有一段30个碱基对的缺失，包括核苷酸168,285至168,256。这些缺失突变体在HD、血管免疫母细胞性淋巴结病、B免疫母细胞性淋巴瘤、外周T细胞淋巴瘤以及两株淋巴母细胞系中被鉴定出来。我们的研究结果揭示，LMP1癌基因3'（羧基末端）区域内优先位点存在高频非随机点突变。这些突变热点与LPD的关联表明它们参与了EBV相关的淋巴瘤发生，并且它们定义了一种具有临床相关性的EBV毒株。
