Major sequence variants in E7 gene of human papillomavirus type 16 from cervical cancerous and noncancerous lesions of Korean women
Major sequence variants in E7 gene of human papillomavirus type 16 from cervical cancerous and noncancerous lesions of Korean women
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DOI：
10.1006/gyno.1997.4756
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发表时间：
1997-08-01
影响因子：
4.7
通讯作者：
Lee, HP
中科院分区：
文献类型：
--
作者：
Song, YS;Kee, SH;Lee, HP
HPV 16基因组编码区和非编码区核苷酸序列变异的地理特异性已有报道。然而，关于HPV 16的这些天然存在的序列变异是否会导致生物学特性的显著差异，如致癌潜力，人们知之甚少。本研究的目的是鉴定来自韩国宫颈癌和非癌病变妇女的HPV 16 E7基因的序列变异，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）和PCR定向测序方法，使用外部一致性引物和内部型特异性引物，检测了157例无宫颈疾病（NCD，n = 87）或宫颈瘤变（宫颈上皮内瘤变3，n = 21;宫颈癌，n = 49）的HPV 16的E7变异体。157例宫颈标本中有42例（NCD 9例，CIN 3 6例，宫颈癌27例）含有HPV 16 E7 DNA，但仅有8例有原型序列。HPV 16 E7基因的四种变体被鉴定。60%的HPV 16型DNA样本中存在647位单核苷酸变异（A → G，Asn → Ser）。第二个最常见的变异，在16.7%的病例中发现，在732（T -> C），789（T -> C）和795（T -> G）位置有三个沉默突变。检测到另外两种变异，一种在宫颈癌患者中，另一种在没有宫颈疾病的患者中。一个在位置666（G -> A）处具有单核苷酸改变，另一个在位置796（T -> C）处具有一个沉默突变。韩国最常见的变异体具有影响与高抗原性和与视网膜母细胞瘤蛋白结合相关的预测氨基酸的核苷酸变化。有一个统计学显着的趋势，这种变异更频繁地检测到宫颈癌病变比非癌病变。这些数据表明，HPV 16 E7基因的天然序列变异体可能具有不同的致癌特性。(C)北京：清华大学出版社.
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. (C) 1997 academic Press.