LINE-1 Methylation Patterns as a Predictor of Postmolar Gestational Trophoblastic Neoplasia

Abstract

Objective. To study the potential of long interspersed element-1 (LINE-1) methylation change in the prediction of postmolar gestational trophoblastic neoplasia (GTN). Methods. The LINE-1 methylation pattern from first trimester placenta, hydatidiform mole, and malignant trophoblast specimens were compared. Then, hydatidiform mole patients from 11999 to 2010 were classified into the following 2 groups: a remission group and a group that developed postmolar GTN. Specimens were prepared for a methylation study. The methylation levels and percentages of LINE-1 loci were evaluated for their sensitivity, specificity, and accuracy for the prediction of postmolar GTN. Results. First, 12 placentas, 38 moles, and 19 malignant trophoblast specimens were compared. The hydatidiform mole group had the highest LINE-1 methylation level (p = 0.003) and the uCuC of LINE-1 increased in the malignant trophoblast group (p ≤ 0.001). One hundred forty-five hydatidiform mole patients were classified as 103 remission and 42 postmolar GTN patients. The %mCuC and %uCmC of LINE-1 showed the lowest p value for distinguishing between the two groups (p < 0.001). The combination of the pretreatment β-hCG level (≥100,000 mIU/mL) with the %mCuC and %uCmC, sensitivity, specificity, PPV, NPV, and accuracy modified the levels to 60.0%, 92.2%, 77.4%, 83.8%, and 82.3%, respectively. Conclusions. A reduction in the partial methylation of LINE-1 occurs early before the clinical appearance of malignant transformation. The %mCuC and %uCmC of LINE-1s may be promising markers for monitoring hydatidiform moles before progression to GTN.

Investigation of epigenetic regulatory networks associated with autism spectrum disorder (ASD) by integrated global LINE-1 methylation and gene expression profiling analyses

“…The methylation level of LINE-1 was measured using COBRA as described in previous reports [ 21 , 22 , 51 , 52 ]. Briefly, genomic DNA was treated with sodium bisulfite using the EZ DNA Methylation-Gold ™ Kit (Zymo Research, Irving, CA, USA) according to the manufacturer’s protocol.…”

Epigenetic modification of long interspersed elements-1 in cumulus cells of mature and immature oocytes from patients with polycystic ovary syndrome

“…Previous studies from our labs [ 9 ] have shown that the long interspersed elements (LINE-1, L1s), a group of genetic elements that are found in large numbers in the human genome, may be associated with several gynaecologic conditions such as endometriosis [ 10 ], gestational trophoblastic neoplasia [ 11 ], cervical intraepithelial neoplasia [ 12 ], and epithelial ovarian cancer [ 13 ]. The methylation changes in LINE-1 might provide insight into the pathogenesis of PCOS.…”

“…For LINE-1 methylation measurement, we selected combined bisulfite restriction analysis (COBRA) instead of pyrosequencing. COBRA for LINE-1 using two restriction enzymes was demonstrated to be able to detect LINE-1 methylation pattern changes, while pyrosequencing can detect only methylation levels [ 11 26 ].…”

Head and neck squamous cell carcinoma drives long interspersed element‐1 hypomethylation in the peripheral blood mononuclear cells

“…In the past, we were able to differentiate LINE-1 methylation patterns of smoked oral epithelial, premalignant lesion of hydatidiform moles, keratinocyte from patients with psoriasis vulgaris, and cancer such as, mucoepidermoid carcinoma, lymph node metastases of head and neck cancers, bladder cancer, and PBMCs of colon cancer (Kitkumthorn, Keelawat, et al, 2012;Kitkumthorn, Tuangsintanakul, et al, 2012;Lertkhachonsuk et al, 2015;Patchsung et al, 2012;Sirivanichsuntorn et al, 2013;Wangsri et al, 2012;Yooyongsatit et al, 2015). In this study, the percentage of unmethylated alleles provided higher efficiency than DNA methylation levels.…”

“…The COBRA technique has been proven to have equivalent precision similar to bisulfite pyrosequencing techniques (Jintaridth & Mutirangura, 2010;Rerkasem et al, 2015). Nevertheless, although pyrosequencing cannot distinguish methylation allele distribution patterns (Pobsook et al, 2011), in some situations, a change in the pattern of the methylation allele distribution can be identified (Lertkhachonsuk, Paiwattananupant, Tantbirojn, Rattanatanyong, & Mutirangura, 2015;Wangsri, Subbalekha, Kitkumthorn, & Mutirangura, 2012).…”