Table 2.
Methylation markers studied in cervical specimens.
| Gene | Number of studies | Methylation frequency (number positive) | Full name | Biological function | ||
|---|---|---|---|---|---|---|
| NL | HGCIN† | Ca | ||||
| DAPK | 22 | 0.068 (33) | 0.296 (158) | 0.582 (659) | Death-associated protein kinase-1 | Serine-threonine kinase; positive mediator of IFN-γ-induced apoptosis |
| RASSF1 | 17 | 0.031 (10) | 0.102 (31) | 0.141 (175) | Ras association (RalGDS/AF-6) domain family member-1 | Ras effector protein; microtubule regulation, cell migration, proliferation and apoptosis |
| CDH1 | 15 | 0.159 (37) | 0.129 (36) | 0.521 (456) | Cadherin 1, E-cadherin | Calcium-dependent cell adhesion glycoprotein |
| CDKN2A/p16 | 15 | 0.049 (17) | 0.131 (26) | 0.220 (187) | Cyclin-dependent kinase inhibitor 2A | Inhibits CDK4 kinase; regulation of cell-cycle control in G1 |
| MGMT | 12 | 0.091 (33) | 0.124 (37) | 0.183 (124) | 0–6 methylguanine-DNA methyltransferase | DNA repair |
| RARB | 12 | 0.045 (15) | 0.130 (40) | 0.343 (169) | Retinoic acid receptor-β | Regulates gene expression in response to thyroid–steroid hormones |
| CADM1 | 10 | 0.256 (43) | 0.385 (106) | 0.657 (236) | Cell adhesion molecule 1 | Intracellular adhesion |
| FHIT | 10 | 0.072 (21) | 0.020 (2) | 0.398 (268) | Fragile histidine triad gene | Diadenosine 5′,5‴-P1, P3-triphosphate hydrolase; purine metabolism |
| TIMP3 | 9 | 0 (0) | 0.107 (6) | 0.189 (82) | TIMP metallopeptidase inhibitor 3 | Matrix metalloproteinase; degradation of the extracellular matrix |
| TERT | 7 | 0.156 (12) | 0.388 (73) | 0.628 (120) | Telomerase reverse transcriptase | Enzymatic component of telomerase; responsible for the addition of short repeats to the ends of chromosomes or telomeres |
| CDH13 | 5 | 0.177 (25) | 0.047 (7) | 0.391 (79) | Cadherin 13, H-cadherin | Calcium-dependent cell adhesion glycoprotein |
| PAX1 | 4 | 0 (0) | 0.356 (36) | 0.917 (33) | Paired box 1 | Pattern formation during embryogenesis |
| TFPI2 | 4 | 0.200 (20) | 0.342 (13) | 0.721 (88) | Tissue factor pathway inhibitor 2 | Regulation of plasmin-mediated matrix remodeling |
| CCNA | 3 | 0.108 (8) | 0.387 (24) | 0.696 (94) | Cyclin A2 | Activates CDK2 kinases; promotes G1/S and G2/M transitions |
| MAL | 3 | 0.098 (4) | 0.577 (71) | 0.942 (227) | T-lymphocyte maturation-associated protein | Candidate linker protein in T-cell signaling; implicated in myelin biogenesis and function in the nervous system; formation, stabilization and maintenance of glycosphingolipid-enriched membrane microdomains |
| TWIST | 3 | 0.0928 (4) | 0.403 (27) | 0.362 (68) | Twist homolog 1 | Transcription factor; differentiation and cell lineage determination |
Inclusion criteria: genes that have been studied in normal, high-grade and cancer samples; genes that showed a low level of methylation (<20%) in normal samples that increased in precancerous lesions and/or cancer samples; genes that have been reported in at least three studies; or genes that have been utilized in a marker panel.
†
Includes CIN2, CIN3 and HSIL in calculations.
Ca: Cervical cancer; HGCIN: High-grade cervical intraepithelial neoplasia; NL: No lesion.