Bergsagel D J, Finegold M J, Butel J S, Kupsky W J, Garcea R L
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital, Boston.
N Engl J Med. 1992 Apr 9;326(15):988-93. doi: 10.1056/NEJM199204093261504.
Ependymomas and papillomas of the choroid plexus occur in early childhood. The ubiquitous human polyomaviruses, BK virus and JC virus, have been associated with the induction of these neoplasms in animal models. A related monkey polyomavirus, simian virus 40 (SV40), is highly tumorigenic in rodents and also induces choroid plexus papillomas.
We tested the possibility that polyomaviruses were associated with these tumors in humans. Tumors from 31 children--20 with choroid plexus neoplasms and 11 with ependymomas--were evaluated for the presence of polyomavirus T-antigen gene sequences by means of amplification with the polymerase chain reaction.
Ten of the 20 choroid plexus tumors and 10 of the 11 ependymomas contained amplification products that preferentially hybridized to probes specific for SV40 viral DNA rather than BK or JC viral DNA. In two specimens, DNA sequencing demonstrated that the amplified sequence was identical to the sequence of that region of the SV40 gene. In three other specimens, amplification with SV40-specific primers revealed a 574-bp segment of the SV40 viral gene. In 7 of 11 tumors examined by immunohistochemical staining, viral T antigen was expressed in the nuclei of the neoplastic cells.
Half of the choroid plexus tumors and most of the ependymomas that we studied contained and expressed a segment of T-antigen gene related to SV40. These results suggest that SV40 or a closely related virus may have an etiologic role in the development of these neoplasms during childhood, as in animal models.
室管膜瘤和脉络丛乳头状瘤发生于儿童早期。普遍存在的人多瘤病毒，BK病毒和JC病毒，在动物模型中与这些肿瘤的诱发有关。一种相关的猴多瘤病毒，猴病毒40（SV40），在啮齿动物中具有高度致瘤性，也可诱发脉络丛乳头状瘤。
我们测试了多瘤病毒与人类这些肿瘤相关的可能性。通过聚合酶链反应扩增，对31名儿童的肿瘤——20例脉络丛肿瘤和11例室管膜瘤——进行多瘤病毒T抗原基因序列检测。
20例脉络丛肿瘤中的10例和11例室管膜瘤中的10例含有扩增产物，这些产物优先与SV40病毒DNA特异性探针杂交，而非BK或JC病毒DNA。在两个标本中，DNA测序表明扩增序列与SV40基因该区域的序列相同。在其他三个标本中，用SV40特异性引物扩增出SV40病毒基因的一个574碱基对片段。在通过免疫组织化学染色检测的11个肿瘤中的7个中，肿瘤细胞核中表达病毒T抗原。
我们研究的脉络丛肿瘤中有一半以及大多数室管膜瘤含有并表达与SV40相关的T抗原基因片段。这些结果表明，如同在动物模型中一样，SV40或一种密切相关的病毒可能在儿童期这些肿瘤的发生中起病因学作用。
