Table 2.
Selected candidate tumor suppressor and cancer genes identified as hypermethylated in cancer. Function is from Gene Ontology. Methylation frequency refers to primary tumors unless stated. ND = Not done. Invariably, bisulfite sequencing was used as an initial assay followed by MSP of a larger number of tumors. COBRA is also used by some researchers.
| Gene Name | Chromosomal Location | Function | Methylation Frequency | References | |
|---|---|---|---|---|---|
| Kidney | Bladder | ||||
| E-cadherin | 16q22.1 | TSG, Cell-cell adhesion | 11% | 36% | [16, 43] |
| H-cadherin | 16q23.3 | Cell adhesion protein; negative regulator of neural cell growth | ND | 29% | [43] |
| Timp-3 | 22q12.3 | Inhibitor of proteolytic matrix metalloproteinase activity | 58-78% | ND | [16, 53] |
| RASSF1A | 3p21.31 | Negative cell cycle regulation | 28-91% | 35-60% | [16, 39, 43, 56-58, 60] |
| GSTP1 | 11q13.2 | Detoxification | <10% | <10% | [16, 27, 63, 68] |
| MGMT | 10q26.3 | DNA repair | 6-8% | 2-5% | [16, 43, 64] |
| DAP-Kinase | 9q34.1 | Positive regulator of apoptosis | None | 4-9% | [27, 41, 43, 68] |
| RARβ2 | 3p24.2 | Transcriptional regulation | 12% | 15-19% | [16, 43, 44, 72] |
| LAMA3 | 18q11.2 | Cell adhesion, Signal transduction | ND | 45% | [73] |
| LAMB3 | 1q32.2 | Mediator of cellular attachment, migration and organization | ND | 25% | |
| LAMC2 | 1q25.3 | Mediator of cellular attachment, migration and organization | ND | 23% | |
| Reprimo | 2q23.3 | Cell cycle control | ND | 19% | [74] |
| FHIT | 3p14.2 | Cell cycle | ND | 11-16% | [43, 75] |
| SPINT2 | 19q13.2 | Inhibitor of HGF activator | 33% | ND | [77] |
| BLU | 3p21.3 | Unknown | 50% cell lines | ND | [78] |
| SFRP1 | 8p11.1 | Modulator of Wnt signaling. | 47-68% | 18-29% | [79-81, 83] |
| SFRP2 | 4q31.3 | Modulator of Wnt signaling. | 53% | 52% | [80, 83] |
| SFRP3 | 2q32.1 | Modulator of Wnt signaling. | >30% | ND | [104] |
| SFRP4 | 7p14.1 | Modulator of Wnt signaling. | 53% | 9% | [80, 83] |
| SFRP5 | 10q24.1 | Modulator of Wnt signaling. | 56% | 37% | [80, 83] |
| DRM/Gremlin | 15q13.3 | Inbibits TGFb signaling | >30% | 51% | [87, 101] |
| RUNX3 | 1p36.11 | Facilitates TGFb signaling | ND | 35% | [87] |
| HPP1 | 2q32.3 | Inbibits TGFb Signaling | ND | 42% | [87] |
| HOXB13 | 17q21.32 | Vertebrate Development | 30% | ND | [88] |
| DAL-1/4.1B | 18p11.31 | Actin Binding Protein | 45% | ND | [89] |
| ABCG2 | 4q22.1 | Xenobiotic transporter | 67% cell lines | ND | [90] |
| XAF1 | 17p13.1 | Zinc ion binding | 10-86% | 89% | [93, 94] |
| IGFBP1 | 7p13 | IGF binding protein | 31% | ND | [95] |
| IGFBP3 | 7p13 | IGF binding protein, inhibitor of cell growth | 37% | ND | [95] |
| COL1A1 | 17q21.33 | Extracellular matrix component; growth and tissue repair | 56% | ND | [95] |
| COLlA2 | 7q21.3 | Extracellular matrix component; growth and tissue repair | ND | 63% | [97] |
| KRT19 | 17q21.2 | Cytoskeleton structure | 38% | ND | [100] |
| CXCL16 | 17p13.2 | Transmembrane chemokine | 42% | ND | [100] |
| UCHL1/PGP9.5 | 4p13 | Processing of ubiquitin precursors and of ubiquitinated proteins | 37-41% | ND | [82, 102] |
| LOXL1 | 15q24.1 | Extracellular matrix | ND | 70% | [105] |
| LOXL4 | 10q24.2 | Extracellular matrix | ND | 40% | [105] |
| TWIST | 7p21.1 | Transcription factor, negative regulation of cellular determination | >20% | >70% | [104, 131] |
| NID2 | 14q22.1 | Cell adhesion, extracellular matrix interaction | ND | >70% | [131] |
| PDLIM4 | 5q31.1 | Protein binding | >30% | ND | [101] |