Craigo J, Hopkins M, DeLucia A
Department of Microbiology/Immunology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272, USA.
Gynecol Oncol. 1995 Dec;59(3):423-6. doi: 10.1006/gyno.1995.9949.
Human papillomavirus (HPV) type 18 DNA was found in an aggressively invasive adenocarcinoma tumor from a woman who had an intact hymen and denied any prior sexual intercourse. The viral DNA was detected within the tumor tissue by polymerase chain reaction (PCR) using consensus primers for the L1 region of oncogenic high-risk genital HPVs. In order to determine mutations within the tumor suppressor gene p53, the gene exons were amplified by PCR followed by single-stranded conformation polymorphism (SSCP) analysis. The appearance of a mutation in exon 8 of the p53 gene suggested by SSCP was directly confirmed by DNA sequencing of the exon. The sequencing showed a single base deletion that may truncate the protein by introducing a early stop codon in the messenger RNA. This early truncation could be expected to affect the proper oligomerization of the p53 protein and hence its DNA-binding activity. The results show that genital oncogenic human papillomaviruses may be passed by nonsexual routes and suggest that the virus may work in concert with p53 mutations to help the infected tissue progress toward invasive cancer.
在一名处女膜完整且否认有过任何性交史的女性的侵袭性腺癌肿瘤中发现了18型人乳头瘤病毒(HPV)DNA。使用致癌性高危生殖器HPV的L1区域的共有引物,通过聚合酶链反应(PCR)在肿瘤组织中检测到病毒DNA。为了确定肿瘤抑制基因p53内的突变,通过PCR扩增基因外显子,随后进行单链构象多态性(SSCP)分析。SSCP提示的p53基因第8外显子中的突变通过该外显子的DNA测序得到直接证实。测序显示单个碱基缺失,这可能通过在信使RNA中引入提前终止密码子而使蛋白质截短。可以预期这种早期截短会影响p53蛋白的正确寡聚化,从而影响其DNA结合活性。结果表明,生殖器致癌性人乳头瘤病毒可能通过非性途径传播,并提示该病毒可能与p53突变协同作用,促使受感染组织发展为浸润性癌。