Comparison of DNA hypermethylation patterns in different types of uterine cancer: Cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma

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Abstract

The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1andTIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant atp< 0.0055), we found that the aberrant hypermethylations ofCDH1andDAPKwere more frequent in CSCCs than in CAs (80.6%vs. 43.3%,p= 0.001; 77.4%vs. 46.7%,p= 0.005), whereasHLTFandTIMP3were more frequently methylated in CAs (3.2%vs. 43.3%,p< 0.001; 8.1%vs. 53.3%,p= 0.001). The hypermethylations ofRASSF1AandAPCwere more frequent in CAs than in CSCCs, but this was not significant (9.7%vs. 33.3%,p= 0.008; and 14.5%vs. 40.0%, respectively,p= 0.009). In addition,RASSF1Ahypermethylation was significantly more frequent in EAs than in CAs (81.0%vs. 33.3%,p= 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms.

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