Table 1. Recently identified methylated tumor suppressor genes in gastric cancer.
| Gene | Chromosomal location | Frequency of methylation (%) |
Basic function | Reference | |
| Tumor tissue | Cell line | ||||
| RASAL1 | 12q23-q24 | 9.5% (2/21) | 60% (6/10) | GAP1 family of GTPase-activating protein, acting as a suppressor of RAS function | [14] |
| EDNRB | 13q22.3 | amean 50.42% | / | G protein coupled receptor superfamily | [15] |
| LMX1a | 1q22-q23 | 82% (41/50) | 100% (5/5) | Nucleotide, transcription, regulation | [16] |
| XRCC1 | 19q13.31 | 76.4% (26/34) | / | Nucleotide, repair, base excision repair | [17] |
| TFPI2 | 7q | 83% (15/18) | 100% (9/9) | Playing a major role in cell migration and tumor invasion | [18] |
| TFF2 | 21q22.3 | 83% (15/18) | / | / | [19] |
| WWOX | 16q23.1 | 33% (24/73) | 40% (2/5) | Putatively involved in regulation of apoptosis | [20] |
| TSP1 | 6p12.3 | 35.4% (34/96) | / | Cysteine-rich secretory protein (CRISP) family, motor/Contractile, structural protein | [21] |
| HOPX | 4q12 | b84% (67/80) | / | Transcription factor | [22] |
| GATA4/5 | 8p23.1/20q13.33 | 53.8% (43/80); 61.3% (49/80) | / | GATA zinc finger transcription factor family | [23] |
| RECK | 9p13.3 | 47.5% (19 /40) | / | Acting as a negative regulator for matrix metalloproteinase 9 and 2 | [24] |
| GADD45G | 9q22.1-q22.2 | c63% (63/100) | / | Ribosomal protein L7AE/gadd45 family, signaling growth factor, DNA damage response and cell growth arrest | [25] |
| LRP1B | 2q21.2 | 61% (45/74) | 100% (4/4) | Low density lipoprotein receptor gene family (LDLR), transducer of extracellular signals, and may be involved in signal transduction | [26] |
| HAI2/SPINT2 | 19q13.2 | 75% ( 30/40) | 100% (4/4) | Kunitz family of serine protease inhibitor, playing an important regulatory role in pericellular activation of hepatocyte growth factor/scatter factor (HGF/SF) | [27] |
| UNC5C | 4q22.3 | 25% ( 9/36) | / | Dependence receptor family, unc-5 family | [28] |
| RELN | 7q22.1 | 100% (15 /15) | 100% (9/9) | Reelin family, signal transduction | [29] |
| Claudin-11 | 3q26.2-q26.3 | 100% (18/18) | 100% (5/5) | Claudin family, adhesion, major structural components of tight junction (TJ) strands | [30] |
| CDH3 | 16q22.1 | 69% (25/36) | / | Cadherin superfamily of calcium dependent cell-cell adhesion glycoproteins | [31] |
| CDH5 | 16q22.1 | 73% (11/15) | 100% (7/7) | Cadherin superfamily of calcium dependent cell-cell adhesion glycoproteins | [32] |
| GRIK2 | 6q16.3 | 70% (19/27) | 75% (3/4) | Glutamate-gated ion channel (TC 1.A.10) family, receptor membrane, transport channel | [33] |
| SLC19A3 | 2q36.3 | 51% (52/101) | 57% (4/7) | Reduced folate family of micronutrient transporter genes, may contribute to resistance to apoptosis in the tumors | [34] |
| PTCMa | 9q22.32 | 32% (55/170) | / | Patched family, signaling, receptor | [35] |
| S0CS6 | 18q22.2 | 46.8% (22/47) | 44.4% (4/9) | SOCS protein family, regulatory, signaling | [36] |
| BTG4 | 11q23.1 | 73.7% (28/38) | 100% (5/5) | Tob/TBG1 family of growth inhibitory gene, antiproliferative activity, being able to induce G1 arrest | [37] |
| Vimentin | 10p13 | 38% (14/37) | / | Intermediate filament family, structural protein, | [38] |
| DLEC1 | 3p22.2 | 34% (30/89) | 100% (17/17) | Tumor suppressor gene(s), putatively involved in regulation of the expression of the telomere | [39] |
| ZIC1 | 3q24 | 94.6% (35/37) | 100% (7/7) | Transcription factor | [40] |
| Hsulf-1 | 8q13.3 | 81.3% (13/16) | 100% (3/3) | Sulfatase family, enzyme | [41] |
| MAL | 2q11.1 | 65.8% (133/202) | / | MAL proteolipid family, cellular trafficking transport | [42] |
| FBLN1 | 22q13.31 | 84% (86/102) | 71% (5/7) | Structural protein | [43] |
| TCF4 | 18q21.2 | dmean 3.3% | / | Basic helix-loop-helix (BHLH) family of transcription factors, Wnt signaling pathway | [44] |
| CACNA2D3 | 3p21.1 | 30% (24/80) | / | Alpha-2/delta subunit family, having voltage-gated ion channel activity | [45] |
| DCBLD2 | 3q12.1 | amean 12.2% | 36.4% (4/11) | Neuropilin family, adhesion | [46] |
| PKD1 | 16p13.3 | amean 19.5% | 72.7% (8/11) | Polycystin family, involved in cell-cell/matrix interaction and the regulation of several signalling pathways linked to cell proliferation | [47] |
| TSPYL5 | 8q22.1 | 63.9% (23/3) | 70% (7/10) | Nucleosome assembly protein (NAP) family, involved in nucleosome assembly | [48] |
| IQGAP2 | 5q13.3 | 47% (28/59) | 33.3% (3/9) | Ras GTPase-activating protein family, Wnt/beta-catenin signaling pathway | [49] |
| TMS1 | 16p12-p11.2 | 32.1% (26/81) | / | CARD containing adaptor protein family, adaptor, signal transduction | [50] |
| DAPK1 | 9q21.33 | 22.2% (18/81) | / | Protein kinase superfamily, enzyme, signaling, adhesion inhibitory effect, inducing death coupling the control of apoptosis to metastasis | [51] |
| NMDAR2B | 12p13.1 | 61% (17/28) | 60% (6/10) | Glutamate-regulated family of ion channels, receptor membrane, transport channel, glutamate signaling pathway | [52] |
| CD99 | Xp22.32 | 16.9% (15/89) | / | CD99 family, adhesion, antigen, signal transduction mediated death signaling (novel death pathway) | [53] |
| ADRA1B | 5q33.1 | 70.6% (24/34) | / | G protein coupled receptor superfamily, signal transduction, mediating its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system | [54] |
| VEGFC | 4q34.3 | 29% (9/31) | 36.4% (4/11) | PDGF/VEGF growth factor family, signal transduction | [55] |
| SMAD4 | 18q21.2 | 5% (4/73) | 0% (0/9) | Dwarfin (DWA/B)/Smad family, DNA associated, transcription factor, critical mediator of TGFB and BMP signaling pathways | [56] |
| NES1/hk10 | 19q13.33 | 90.9% (10/11) | 71.4% (5/7) | Kallikrein family, peptidase S1 family, enzyme | [57] |
| IGFBP3 | 7p12.3 | 67% (16/24) | 46% (6/13) | Sterol desaturase family, signaling cytokine growth factor | [58] |
| DFNA5 | 7p15.3 | 52% (46/89) | 100% (12/12) | Gasdermin family, plays a role in the TP53-regulated cellular response to genotoxic stress probably by cooperating with TP53 | [59] |
| LIMS2 | 2q14.3 | 53% (51/96) | 80% (8/10) | PINCH protein family, novel LIM domain-containing gene, adhesion, regulatory | [60] |
| HLTF | 3q24 | 38% (98/256) | / | SWI/SNF family of chromatin remodeling complex, actin-dependent regulator of chromatin structure CHFR-mediated downregulation of HLTF may help protect against cancer | [61] |
| BMP2 | 20p12.3 | 42.9% (24/56) | 50% (2/4) | Transforming growth factor-beta (TGFB) superfamily, signaling growth factor, activating PI-3 kinase/Akt pathway | [62] |
| EBF3 | 10q26.3 | 40.4% (42/104) | 60% (6/10) | Cell cycle progression and apoptosis | [63] |
| SST | 3q28 | 93% (30/32) | 100% (7/7) | A primary inhibitor of gastrin-stimulated gastric acid secretion | [64] |
| HIN1 | 5q35.3 | 57.8% (26/45) | 80% (4/5) | Uteroglobin/Clara cell secretory protein family, secretory, signaling cytokine, tumor suppressor may be mediated through the AKT signaling pathway | [65] |
| IRX1 | 5p15.33 | 51.9% (8/15) | 100% (7/7) | TALE/IRO homeobox family, transcription factor | [67] |
| CMTM3 | 16q22.1 | 44% (28/63) | 68.8% (11/16) | Chaperone/stress, signaling | [68] |
| S0X2 | 3q26.33 | 16.2% (12/74) | 20% (2/10) | Transcription factor, can inhibit beta-catenin-driven reporter gene expression | [69] |
| ZNF382 | 19q13.12 | 63.6%(7/11) | 100% (15/15) | Transcription factor | [70] |
| UCHL1 | 4p13 | 77% (53/69) | 88.2% (15/17) | Ubiquitin carboxyl-terminal hydrolase family 1, enzyme, transcription factor | [71] |
| hSRBC | 11p15.4 | 41% (46/111) | 73% (11/15) | STICK (substrates that interact with C-kinase) superfamily of PKC-binding protein, | [72] |
| OPCML | 11q25 | 64% (7/11) | 100% (17/17) | Immunoglobulin superfamily, adhesion | [73] |
| PLCD1 | 3p22.2 | 62% (61/98) | 84% (16/19) | Enzyme, signal transduction | [77] |
| DLC1-i4 | 8p22 | 82% (9/11) | 12.5% (2/16) | RhoA pathway | [80] |
| Sox17 | 8q11.23 | / | 100% (2/2) | Transcription factor, | [92] |
| POPDC3 | 6q21 | 64.5% (15/18) | 73% (8/11) | Unknown/unspecified | [93] |
| BVES | 6q21 | 69% (53/76) | 73% (8/11) | Interacting with GEFT, a GEF for Rho-family GTPases, and colocalizing in adult skeletal muscle | [93] |
| PCDH10 | 4q28.3 | 82% (85/104) | 94% (16/17) | Protocadherin subfamily, cadherin superfamily of calcium dependent cell-cell adhesion glycoproteins | [95] |
| FBP1 | 9q22.32 | 33% (33/101) | 57% (4/7) | FBPase class 1 family, enzyme, catalyzing the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate | [97] |
| LRRC3B | 3p24.1 | / | 90.9% (10/11) | IFN Signaling gene | [98] |
a, pyrosequencing; b, Q-MSP; c, high-resolution melting (HRM) analysis; d, methylight; e, bisulfit sequencing.