Song Y S, Kee S H, Kim J W, Park N H, Kang S B, Chang W H, Lee H P
Department of Obstetrics and Gynecology, Seoul National University Hospital, Korea.
Gynecol Oncol. 1997 Aug;66(2):275-81. doi: 10.1006/gyno.1997.4756.
Geographic specificity of nucleotide sequence variations in the coding and noncoding regions of HPV 16 genome has been reported. Little has been known, however, regarding whether these naturally occurring sequence variations of HPV 16 may result in marked differences in biological properties, such as oncogenic potential. This study was performed to identify sequence variants in the HPV 16 E7 gene derived from Korean women with cervical cancerous and noncancerous lesions, and to assess the association between the sequence variant and the cervical cancer. We examined E7 variants of HPV 16 in a total of 157 patients with no cervical disease (NCD, n = 87) or cervical neoplasia (cervical intraepithelial neoplasia 3, n = 21; cervical carcinoma, n = 49), using the nested polymerase chain reaction (PCR) and the PCR-directed sequencing methods with outer consensus and inner type-specific primers. Forty-two (NCD, n = 9; CIN 3, n = 6; cervical carcinoma, n = 27) of 157 cervical samples contained HPV 16 E7 DNA, but only 8 had prototype sequences. Four variants of the HPV 16 E7 gene were identified. The variant with a single nucleotide change at position 647 (A --> G, Asn --> Ser) was found in about 60% of DNA samples with HPV 16. The second most common variant, found in 16.7% of cases, had three silent mutations at positions 732 (T --> C), 789 (T --> C), and 795 (T --> G). Two other variants were detected, one in a patient with cervical cancer and the other in a patient with no cervical disease. One had a single nucleotide change at position 666 (G --> A) and the other had one silent mutation at position 796 (T --> C). The most common variant in Korea has a change of nucleotide affecting the predicted amino acid related with high antigenicity and binding to retinoblastoma protein. There was a statistically significant trend for this variant to be more frequently detected in cancerous lesions of the uterine cervix than in noncancerous lesions. These data suggest that naturally occurring sequence variants of HPV 16 E7 gene may have different oncogenic properties.
已有报道称人乳头瘤病毒16型（HPV 16）基因组编码区和非编码区核苷酸序列变异具有地理特异性。然而，关于HPV 16这些自然发生的序列变异是否会导致生物学特性（如致癌潜力）的显著差异，人们了解甚少。本研究旨在鉴定来自韩国宫颈癌和非癌性病变女性的HPV 16 E7基因中的序列变异，并评估序列变异与宫颈癌之间的关联。我们使用巢式聚合酶链反应（PCR）以及带有外部共有引物和内部型特异性引物的PCR定向测序方法，检测了总共157例无宫颈疾病（NCD，n = 87）或宫颈肿瘤（宫颈上皮内瘤变3级，n = 21；宫颈癌，n = 49）患者的HPV 16 E7变异体。157份宫颈样本中有42份（NCD，n = 9；CIN 3，n = 6；宫颈癌，n = 27）含有HPV 16 E7 DNA，但只有8份具有原型序列。鉴定出了HPV 16 E7基因的4种变异体。在约60%的HPV 16 DNA样本中发现了在第647位有单核苷酸变化（A→G，天冬酰胺→丝氨酸）的变异体。第二常见的变异体在16.7%的病例中被发现，在第732位（T→C）、789位（T→C）和795位（T→G）有三个沉默突变。还检测到另外两种变异体，一种在宫颈癌患者中发现，另一种在无宫颈疾病的患者中发现。一种在第666位有单核苷酸变化（G→A），另一种在第796位有一个沉默突变（T→C）。韩国最常见的变异体有一个核苷酸变化，影响与高抗原性及与视网膜母细胞瘤蛋白结合相关的预测氨基酸。在子宫颈癌性病变中比在非癌性病变中更频繁地检测到这种变异体，这一趋势具有统计学意义。这些数据表明，HPV 16 E7基因自然发生地序列变异可能具有不同的致癌特性。
