摘要
通过检测 E6变体在 HPV16阳性的宫颈非典型增生 (CIN)和宫颈浸润癌 (ICC)患者中的分布 ,研究其致癌能力。方法 :用 PCR和双脱氧终止荧光法检测了 42例 E6基因点突变及其编码氨基酸改变 ,统计分布差异。结果 :2例 (5 % )为原型 ,40例 (95 % )的 E6 DNA序列中含有 1至 3个点突变 ,导致 13类 E6氨基酸残基改变 ,组合成 17种 (94% ) HPV16变体。出现频率较高的 4种变体在 CIN和 ICC病例中共同存在 ,分布无显著性差异(P>0 .0 5 )。DNA的点突变数在 CIN和 ICC病例中的分布也无显著性差异 (P>0 .0 5 )。结论 :HPV16 E6的变体多于原型 ,但是变体和原型的致癌能力没有明显差别。
This study sought to clarify whether HPV16 E6 variants are obviously more oncogenic than the prototype by detecting the frequencies of E6 variants in both cervical intraepithelial neoplasia(CIN) and invasive cervical carcinoma(ICC). 42 patients with CIN or ICC and HPV16 positive were selected and investigated for the E6 genes for mutations. PCR amplified products were sequenced by the fluorescent dideoxy termination method. Frequencies of E6 variants and prototype were analyzed for differences in both CIN and ICC The results showed that 40(95%) patients harbored one to three point mutations of E6 gene and only two (5%) patients harbored the prototype. Of 14 kinds of point mutation, 13 led to amino acid residue substitution. The residue substitutions of high frequency were aspartate 25 glutamic acid (i.e. substitution of amino acid in position 25 with a change from aspartate to glutamic acid, the same below), Leucine 83 Valine,Glutamic acid 113 Aspartate and Leucine 115 Proline. These residue substitutions existed in both CIN and ICC.No significant difference in the distribution of these residue substitutions was noted between CIN and ICC ( P >0.05). In addition no significant difference in the distribution of the number of DNA mutation was observed between CIN and ICC ( P >0.05). Otherwise, seven kinds of residue substitution were of low frequency. Of them, two and five existed in CIN and ICC respectively. Since a patient harbored zero to three residue substitutions, these 13 kinds of residue substitution created 17 types of E6 variants. These result indicate that HPV16 E6 variants are more prevalent than the prototype. There is no significant difference in the distribution of E6 variants of high frequency between CIN and ICC, suggesting that the E6 variants do not generate significant difference in their carcinogenesis.
出处
《华西医科大学学报》
CSCD
2000年第4期511-514,共4页
Journal of West China University of Medical Sciences