Wang J, Garcea R L
University of Colorado School of Medicine, Department of Pediatrics, Denver 80262, USA.
Dev Biol Stand. 1998;94:13-21.
This report reviews recent observations regarding the association of simian virus 40 (SV40) DNA sequences with brain and bone tumours of childhood [1-3]. Our initial investigation was suggested by the tumorigenicity of SV40 in animals, and the transgenic mouse expression of SV40 large T-antigen in which all animals developed choroid plexus (CP) tumours. Polymerase chain reaction (PCR) analysis and DNA sequencing demonstrated SV40-like DNA sequences, amplified from the "Rb-pocket" binding domain of the viral large T-antigen, in 10/20 CP and 10/11 ependymoma tumours of children. The PCR analysis was subsequently extended to three additional regions of the viral genome: the carboxy-terminal region of large T-antigen, the viral enhancer/origin, and the VP1 gene. All amplified products were related to SV40 sequences. Furthermore, because one individual in the original brain tumour study was a member of a Li-Fraumeni kindred, 151 DNA samples from such families were analysed. Only 18 were positive for viral sequences and 11 of these were isolated from individuals with osteosarcomas. This observation led to a further analysis of DNA from bone tumours, in which 54/160 samples contained SV40-like sequences. These studies associate SV40-like sequences with human CP, ependymoma, and bone tumours. A causal relationship to human oncogenesis remains a subject for further study.
本报告回顾了近期关于猿猴病毒40（SV40）DNA序列与儿童脑肿瘤和骨肿瘤之间关联的观察结果[1-3]。我们最初的研究是受SV40在动物中的致瘤性以及转基因小鼠中SV40大T抗原的表达所启发，在转基因小鼠中所有动物都发生了脉络丛（CP）肿瘤。聚合酶链反应（PCR）分析和DNA测序显示，在20例儿童CP肿瘤中的10例以及11例室管膜瘤肿瘤中的10例中，从病毒大T抗原的“Rb口袋”结合域扩增出了类似SV40的DNA序列。随后，PCR分析扩展到病毒基因组的另外三个区域：大T抗原的羧基末端区域、病毒增强子/起源区域以及VP1基因。所有扩增产物均与SV40序列相关。此外，由于最初脑肿瘤研究中的一名个体是李-弗劳梅尼家族的成员，因此对来自此类家族的151份DNA样本进行了分析。只有18份样本的病毒序列呈阳性，其中11份是从骨肉瘤患者中分离出来的。这一观察结果促使对骨肿瘤的DNA进行进一步分析，在160份样本中有54份含有类似SV40的序列。这些研究将类似SV40的序列与人类CP肿瘤、室管膜瘤和骨肿瘤联系起来。与人类肿瘤发生的因果关系仍有待进一步研究。
