The CpG island methylator phenotype increases the risk of high-grade squamous intraepithelial lesions and cervical cancer

Clinical Epigenetics

Jaqueline Loaeza-Loaeza¹  Daniel Hernández-Sotelo¹  Oscar del Moral-Hernández²  Yaneth Castro-Coronel³  Roberto Dircio-Maldonado⁴  Berenice Illades-Aguiar⁴  Julio Ortiz-Ortiz⁴  Marco A. Leyva-Vázquez⁴ 

[1] Laboratory of Cancer Epigenetics, School of Chemical and Biological Sciences, Autonomous University of Guerrero, Av. Lázaro Cárdenas S/N Col. Haciendita, 39070, Chilpancingo, Guerrero, Mexico;Laboratory of Cancer Virology, School of Chemical and Biological Sciences, Autonomous University of Guerrero, Av. Lázaro Cárdenas S/N Col. Haciendita, 39070, Chilpancingo, Guerrero, Mexico;Laboratory of Cytopathology and Histochemistry, School of Chemical and Biological Sciences, Autonomous University of Guerrero, Av. Lázaro Cárdenas S/N Col. Haciendita, 39070, Chilpancingo, Guerrero, Mexico;Laboratory of Molecular Biomedicine, School of Chemical and Biological Sciences, Autonomous University of Guerrero, Av. Lázaro Cárdenas S/N Col. Haciendita, 39070, Chilpancingo, Guerrero, Mexico;

关键词: CpG;    Methylation;    Squamous intraepithelial lesion;    Cervical cancer;   

DOI  :  10.1186/s13148-021-01224-0

来源: Springer

【 摘 要 】

BackgroundHigh-risk human papillomavirus (HR-HPV) infection is the main cause of cervical cancer, but additional alterations are necessary for its development. Abnormal DNA methylation has an important role in the origin and dissemination of cervical cancer and other human tumors. In this work, we analyzed the methylation of eight genes (AJAP1, CDH1, CDH13, MAGI2, MGMT, MYOD1, RASSF1A and SOX17) that participate in several biological processes for the maintenance of cell normality. We analyzed DNA methylation by methylation-specific PCR (MSP) and HPV infection using the INNO‑LiPA genotyping kit in 59 samples diagnostic of normal cervical tissue (non-SIL), 107 low-grade squamous intraepithelial lesions (LSILs), 29 high-grade squamous intraepithelial lesions (HSILs) and 51 cervical cancers (CCs).ResultsWe found that all samples of LSIL, HSIL, and CC were HPV-positive, and the genotypes with higher frequencies were 16, 18, 51 and 56. In general, the genes analyzed displayed a significant tendency toward an increase in methylation levels according to increasing cervical lesion severity, except for the CDH13 gene. High CpG island methylator phenotype (CIMP) was associated with a 50.6-fold (95% CI 4.72–2267.3)-increased risk of HSIL and a 122-fold risk of CC (95% CI 10.04–5349.7).ConclusionsWe found that CIMP high was significantly associated with HSIL and CC risk. These results could indicate that CIMP together with HR-HPV infection and other factors participates in the development of HSIL and CC.

【 授权许可】

CC BY