Lestou V S, De Braekeleer M, Strehl S, Ott G, Gadner H, Ambros P F
Children's Cancer Research Institute, St Anna Kinderspital, Vienna, Austria.
Genes Chromosomes Cancer. 1993 Sep;8(1):38-48. doi: 10.1002/gcc.2870080108.
In order to examine the role of Epstein-Barr virus (EBV) in the immortalization of human B lymphocytes and in the pathogenesis of lymphoid malignancies, we investigated whether the EBV integration into the human genome is randomly distributed or whether the virus integrates preferentially at certain sites. Twelve in vitro immortalized human lymphoblastoid cell lines (LCLs), two in vivo infected LCLs, and one Burkitt's lymphoma cell line (EB2) were examined by non-radioactive in situ hybridization (ISH) with a biotinylated EBV probe. Recurrent hybridization sites were detected in all 15 cell lines. The chromosomes frequently carrying the EBV genome were chromosomes 1, 2, 4, and 5. In more than 70 chromosomal bands, a greater number of integration sites than expected was found (p < 0.05). Approximately half of these bands were involved in the majority of the cell lines (for example, 1p31, 1q43, 2p22, 3q28, 4q13, 5p14, 5q12, and 11p15) whereby band 5p14 was involved in all LCLs analyzed. Virtually no viral integrations were found on the sex chromosomes (X, Y). The majority of the EBV integrations was found in G-band-positive material (p < 0.0001). Thus, our findings clearly show that EBV integrates into the human genome in a non-random manner.
为了研究爱泼斯坦-巴尔病毒（EBV）在人B淋巴细胞永生化及淋巴恶性肿瘤发病机制中的作用，我们调查了EBV整合到人基因组中是随机分布的，还是该病毒优先整合于某些特定位点。采用生物素化的EBV探针，通过非放射性原位杂交（ISH）技术检测了12个人体外永生化淋巴母细胞系（LCLs）、2个体内感染的LCLs及1个伯基特淋巴瘤细胞系（EB2）。在所有15个细胞系中均检测到重复杂交位点。频繁携带EBV基因组的染色体为1号、2号、4号和5号染色体。在70多条染色体带中，发现的整合位点数多于预期（p<0.05）。这些带中约一半存在于大多数细胞系中（例如，1p31、1q43、2p22、3q28、4q13、5p14、5q12和11p15），其中5p14带存在于所有分析的LCLs中。在性染色体（X、Y）上几乎未发现病毒整合。大多数EBV整合位于G带阳性物质中（p<0.0001）。因此，我们的研究结果清楚地表明，EBV以非随机方式整合到人基因组中。
