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高危型宫颈鳞状上皮内病变中p16INK4A基因甲基化与人乳头瘤病毒的存在情况。

The presence of methylation of the p16INK4A gene and human papillomavirus in high-grade cervical squamous intraepithelial lesions.

作者信息

Furtado Yara L, Almeida Gutemberg, Lattario Fernanda, Silva Katia S, Maldonado Paula, Silveira Filomena A, do Val Isabel C, Fonseca Renata, Carvalho Maria da Gloria

机构信息

Institute of Gynecology, Gynecology Institute, Surgery Post-Graduation Program, Federal University of Rio de Janeiro, Rua Moncorvo Filho No. 90, Centro, Rio de Janeiro, RJ, Brazil.

出版信息

Diagn Mol Pathol. 2010 Mar;19(1):15-9. doi: 10.1097/PDM.0b013e3181aa8f64.

Abstract

Methylation is a chemical modification in which a methyl group (CH3) is added to the cytosine in the promoter region of the gene. It involves a very frequent epigenetic event that is found in many human cancers. Currently, there is no consensus on whether methylation of the p16 gene could be used as a biomarker in cervical intraepithelial neoplasia. The authors studied the presence of methylation of the p16 gene and human papillomavirus (HPV) DNA, and a possible relationship between them in high-grade squamous intraepithelial lesions of the cervix. This case-control study analyzed 27 high-grade squamous intraepithelial lesion samples and 20 normal cytology samples. To detect p16 methylation, methylation-specific polymerase chain reaction was used, and for HPV DNA detection the polymerase chain reaction was performed by using MY09/MY11 and GP5+/GP6+ consensus primers. The presence of methylation of the promoter region of the p16INK4a gene was detected in 55.6% of the samples from the case group, whereas it was detected only in 20% of the samples from the control group (P=0.005). HPV DNA was found in 66.7% of the samples from the case group, whereas only 15% from the control group (P=0.0001). The relationship between the presence of methylation of the p16 gene and HPV DNA did not prove statistically significant in the case group (P=0.67) or the control group (P=0.51). In conclusion, the presence of methylation of the p16 gene constituted an occurrence that was early but independent of the presence of HPV DNA.

摘要

甲基化是一种化学修饰,其中甲基基团(CH3)被添加到基因启动子区域的胞嘧啶上。它涉及一种在许多人类癌症中都很常见的表观遗传事件。目前,关于p16基因的甲基化是否可作为宫颈上皮内瘤变的生物标志物尚无共识。作者研究了p16基因甲基化和人乳头瘤病毒(HPV)DNA的存在情况,以及它们在宫颈高级别鳞状上皮内病变中的可能关系。这项病例对照研究分析了27个高级别鳞状上皮内病变样本和20个正常细胞学样本。为了检测p16甲基化,使用了甲基化特异性聚合酶链反应,而对于HPV DNA检测,则使用MY09/MY11和GP5+/GP6+共有引物进行聚合酶链反应。在病例组的55.6%的样本中检测到p16INK4a基因启动子区域的甲基化,而在对照组的样本中仅在20%中检测到(P = 0.005)。在病例组的66.7%的样本中发现了HPV DNA,而对照组中仅为15%(P = 0.0001)。在病例组(P = 0.67)或对照组(P = 0.51)中,p16基因甲基化的存在与HPV DNA之间的关系在统计学上并不显著。总之,p16基因甲基化的存在是一种早期出现的情况,但独立于HPV DNA的存在。

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