Potential applications of DNA methylation testing technology in female tumors and screening methods. Biochimica et biophysica acta. Reviews on cancer DNA methylation is a common epigenetic modification, and the current commonly used methods for DNA methylation detection include methylation-specific PCR, methylation-sensitive restriction endonuclease-PCR, and methylation-specific sequencing. DNA methylation plays an important role in genomic and epigenomic studies, and combining DNA methylation with other epigenetic modifications, such as histone modifications, may lead to better DNA methylation. DNA methylation also plays an important role in the development of disease, and analyzing changes in individual DNA methylation patterns can provide individualized diagnostic and therapeutic solutions. Liquid biopsy techniques are also increasingly well established in clinical practice and may provide new methods for early cancer screening. It is important to find new screening methods that are easy to perform, minimally invasive, patient-friendly, and affordable. DNA methylation mechanisms are thought to have an important role in cancer and have potential applications in the diagnosis and treatment of female tumors. This review discussed early detection targets and screening methods for common female tumors such as breast, ovarian, and cervical cancers and discussed advances in the study of DNA methylation in these tumors. Although existing screening, diagnostic, and treatment modalities exist, the high morbidity and mortality rates of these tumors remain challenging. 10.1016/j.bbcan.2023.188941

Analysis of DNA methylation in endometrial biopsies to predict risk of endometrial cancer. Multinu Francesco,Chen Jun,Madison Joseph D,Torres Michelle,Casarin Jvan,Visscher Daniel,Shridhar Viji,Bakkum-Gamez Jamie,Sherman Mark,Wentzensen Nicolas,Mariani Andrea,Walther-Antonio Marina Gynecologic oncology OBJECTIVE:To determine whether analysis of methylated DNA in benign endometrial biopsy (EB) specimens is associated with risk of endometrial cancer (EC). METHODS:We identified 23 women with EBs performed at Mayo Clinic diagnosed as normal (n = 14) or hyperplasia (n = 9) and who later developed endometrial cancer after a median interval of 1 year. Cases were matched 1:1 with patients with benign EBs who did not develop EC (controls) by histology of benign EB (normal endometrium vs. endometrial hyperplasia without atypia), date of EB, age at EB, and length of post-biopsy follow-up. DNA extracted from formalin-fixed paraffin-embedded tissues underwent pyrosequencing to determine percent methylation of promoter region CpGs at 26 loci in 4 genes (ADCYAP1, HAND2, MME, RASSF1A) previously reported as methylated in EC. RESULTS:After pathologic review, 23 matched pairs of cases and controls were identified (14 normal, 9 hyperplasia without atypia per group). Among cases, median time from benign EB to EC was 1 year (range 2 days - 9.2 years). We evaluated 26 CpG sites within 4 genes and found a consistent trend of increasing percentage of methylation from control to case to EC for all CpGs. At the gene-level, mean methylation events of ADCYAP1 and HAND2 in cases were significantly higher than control (p = 0.015 and p = 0.021, respectively). Though the other genes did not reach statistical significance, we observed an increased methylation trend among all genes. Area-under-curve (AUC) calculations (predicting future development of EC in the setting of benign EB) for ADCYAP1 and HAND2 were 0.71 (95% CI 0.55-0.88) and 0.83 (95% CI 0.64-1, respectively). CONCLUSIONS:This proof-of-principle study provides evidence that specific methylation patterns in benign EB correlate with future development of EC. 10.1016/j.ygyno.2019.12.023

Endometrial Cancer Detection by DNA Methylation Analysis in Cervical Papanicolaou Brush Samples. Technology in cancer research & treatment Endometrial cancer (EC) is the leading gynecological cancer worldwide, yet current EC screening approaches are not satisfying. The purpose of this retrospective study was to evaluate the feasibility and capability of DNA methylation analysis in cervical Papanicolaou (Pap) brush samples for EC detection. We used quantitative methylation-sensitive PCR (qMS-PCR) to determine the methylation status of candidate genes in EC tissue samples, as well as cervical Pap brushes. The ability of RASSF1A and HIST1H4F to serve as diagnostic markers for EC was then examined in cervical Pap brush samples from women with endometrial lesions of varying degrees of severity. Methylated RASSF1A and HIST1H4F were found in EC tissues. Further, methylation of the two genes was also observed in cervical Pap smear samples from EC patients. Methylation levels of RASSF1A and HIST1H4F increased as endometrial lesions progressed, and cervical Pap brush samples from women affected by EC exhibited significantly higher levels of methylated RASSF1A and HIST1H4F compared to noncancerous controls ( < .001). Receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses revealed RASSF1A and HIST1H4F methylation with a combined AUC of 0.938 and 0.951 for EC/pre-EC detection in cervical Pap brush samples, respectively. These findings demonstrate that DNA methylation analysis in cervical Pap brush samples may be helpful for EC detection, broadening the scope of the commonly used cytological screening. Our proof-of-concept study provides new insights into the field of clinical EC diagnosis. 10.1177/15330338241242637

Analysis of , , and Gene Methylation in Early Endometrial Cancer for Prediction of Medical Treatment Outcomes. International journal of molecular sciences An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AEH), undergoing organ-preserving treatment, was conducted. OBJECTIVE OF THE STUDY:To determine , , and gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. MATERIALS AND METHODS:A total of 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC ( = 28) and AEH ( = 13), willing to preserve reproductive function, were studied; 18 specimens of uterine cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. RESULTS:All 13 women with AEH had a complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 ( = 28), 14 patients had a complete response (EC CR group) and 14 did not (EC non-CR group). It was found that all groups had statistically significant differences in gene methylation levels compared to the control group ( < 0.001) except for the EC CR group ( = 0.21). The -value for the difference between EC CR and EC non-CR groups was <0.001. The differences in gene methylation levels between the control and study groups were also significantly different ( < 0.001), except for the AEH group ( = 0.21). For the difference between EC CR and EC non-CR groups, the -value was 0.43. For gene methylation levels, statistically significant differences were found between the control and EC non-CR groups ( < 0.001), and the control and EC comparison groups ( = 0.005). When comparing the EC CR group with EC non-CR group, the -value for this gene was <0.001. The simultaneous assessment of and genes methylation allowed for an accurate distinction between EC CR and EC non-CR groups (AUC = 0.96). CONCLUSION:The assessment of and gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), scheduled for medical treatment, can predict the treatment outcome. 10.3390/ijms25094892