Table 1.
Gene methylation frequencies in RCC
| Gene | Locus | Mean RCC methylation (%) | Number of tumors analyzed | Range across multiple studies (%) | ccRCC (%) | pRCC (%) | Adj normal methylation* % (n) | References |
|---|---|---|---|---|---|---|---|---|
| APAF1 | 12q23 | 98 | 170 | 97-100 | 98 | - | 9 (80) | [106,107] |
| APC | 5q21-22 | 17 | 253 | 14-29 | 16 | 32 | 7 (72) | [34,40-43] |
| BNC1 | 15q25 | 46 | 59 | - | - | - | 5 (20) | [63] |
| BTG3 | 21q11.2-21.1 | 70 | 20 | - | - | - | 0 (20) | [108] |
| CASP8 | 2q33-34 | 6 | 139 | 0-16 | 0 | - | - | [53,107] |
| CDH1 | 16q22.1 | 35 | 229 | 11-80 | 83 | 69 | 87 (62) | [33,41-43,53] |
| CDH13 | 16q24.2-24.3 | 3 | 40 | - | - | - | - | [53] |
| COL14A1 | 8q24 | 44 | 41 | - | - | - | 5 (20) | [63] |
| COL15A1 | 9q22 | 53 | 65 | - | - | - | 30 (30) | [63] |
| COL1A1 | 17q21.31-22 | 57 | 30 | - | 65 | 40 | - | [106] |
| CRBP1 | 3q21-22 | 9 | 22 | - | - | - | - | [54] |
| CST6 | 11q13 | 46 | 61 | - | - | - | 11 (35) | [63] |
| CXCL16 | 17p13.2 | 42 | 62 | - | 43 | 40 | 43 (21) | [109] |
| DAL-1/4.1B | 18p11.3 | 45 | 55 | - | 45 | - | - | [110] |
| DAPK1 | 9q34.1 | 35 | 219 | 24-41 | 38 | - | - | [54,108,111] |
| DKK1 | 10q11.2 | 44 | 62 | 0-52 | 44 | - | 8 (62) | [63,65] |
| DKK2 | 4q25 | 58 | 52 | - | 58 | - | 6 (52) | [64] |
| DKK3 | 11p15.2 | 50 | 62 | - | 53 | - | 16 (62) | [62] |
| DLC1 | 8p22-21.3 | 35 | 34 | - | - | - | 3 (34) | [112] |
| ESR1 | 6q25.1 | 69 | 65 | - | 67 | 77 | 77 (62) | [43] |
| ESR2 | 14q23.2 | 53 | 65 | - | 56 | 46 | 43 (62) | [43] |
| FHIT | 3p14.2 | 53 | 87 | 52-53 | 53 | 54 | 52 (0-69) (82) | [43,53] |
| FLCN | 17p11.2 | 9 | 120 | 0-33 | 21 | - | - | [113-115] |
| GREM1 | 15q13 | 24 | 165 | 20-41 | 20 | - | 15 (79) | [63,101] |
| GSTP1 | 11q13 | 10 | 177 | 8-12 | 6 | 15 | 0 (72) | [33,42,43] |
| HOXB13 | 17q21.2 | 30 | 50 | - | - | - | 0 | [102] |
| IGFBP1 | 7p14-12 | 30 | 30 | - | 35 | 20 | - | [106] |
| IGFBP3 | 7p14-12 | 12 | 120 | 3-37 | 13 | 40 | - | [108,116] |
| JUP | 17q21 | 91 | 54 | - | - | 11 | 11 (54) | [100] |
| KTN19 | 17q21.2 | 38 | 66 | - | 39 | 33 | 14 (22) | [109] |
| LOXL1 | 15q24 | 35 | 23 | - | - | - | 24 (17) | [63] |
| LSAMP | 3q13.2-21 | 26 | 53 | - | 26 | - | - | [67] |
| MDRI | 7q21.1 | 86 | 65 | - | 87 | 85 | 97 (62) | [43] |
| MGMT | 10q26 | 8 | 225 | 2-33 | 2 | 0 | 0 (62) | [33,41-43,54] |
| MT1G | 16q13 | 20 | 25 | - | - | - | - | [54] |
| p14ARF | 9p21 | 33 | 299 | 17-68 | 36 | 40 | 20 | [33,34,40,43] |
| p16INK4 | 9p21 | 11 | 407 | 0-80 | 10 | 13 | 0 (87) | [34,35,40-43,54,81] |
| PDLIM4 | 5q31 | 43 | 41 | - | - | - | 0 (22) | [63] |
| PML | 15q22 | 3 | 90 | - | 3 | - | - | [107] |
| PTGS2 | 1q25.2-25.3 | 95 | 65 | - | 96 | 92 | 100 (62) | [43] |
| RARB | 3p24 | 13 | 206 | 0-53 | 2 | 0 | 0 (77) | [34,41-43,54] |
| RASSF1 | 3p21.3 | 51 | 735 | 28-91 | 59 | 75 | 48 (0-100)(174) | [34,35,38,40-46] |
| RASSF5 | 1q32.1 | 28 | 79 | 19-32 | - | - | - | [54,67] |
| ROBO1 | 3p12 | 18 | 44 | - | 18 | - | - | [117] |
| RPRM | 2q23 | 44 | 52 | - | - | - | 18 (44) | [63] |
| SDHB | 1p36.1-35 | 4 | 25 | - | - | - | - | [53] |
| SFRP1 | 8p12-11.1 | 47 | 234 | 34-80 | 50 | 18 | 5 (152) | [59-63] |
| SFRP2 | 4q31.3 | 53 | 62 | - | 56 | - | 10 (62) | [62] |
| SFRP4 | 7p14-13 | 53 | 62 | - | 56 | - | 15 (62) | [62] |
| SFRP5 | 10q24.1 | 57 | 62 | - | 59 | - | 15 (62) | [62] |
| SLIT2 | 4q15.2 | 25 | 48 | - | - | - | 8 (12) | [118] |
| SPINT2 | 19q13.2 | 38 | 118 | - | 30 | 45 | 5 (38) | [70] |
| TIMP3 | 22q12.1-13.2 | 51 | 289 | 20-78 | 36 | 32 | 14 (104) | [34,40-43,119] |
| TU3A | 3p21.1 | 39 | 61 | - | 42 | 25 | 0 (24) | [49] |
| UCHL1 | 4p14 | 38 | 32 | - | - | - | 0 (32) | [116] |
| VHL | 3p26-25 | 16 | 740 | 8-31 | 14 | 16 | 0 | [5,9,33-36,40] |
| WIF1 | 12q14.3 | 73 | 62 | - | 76 | 23 (62) | [62] | |
| XAF1 | 17p13.2 | 12 | 84 | 8-50 | - | - | 0 (4) | [120,121] |
*Where the range of methylation in adjacent (Adj) normal tissue is high across multiple studies, this range is indicated in parentheses before the number analyzed. Abbreviations: APAF1, apoptotic protease activating factor 1; APC, adenomatous polyposis coli; BNC1, basonuclin 1; BTG3, B-cell translocation gene 3; CASP8, caspase 8; CDH1, cadherin 1; CDH13, cadherin 13; COL, collagen; CRBP, retinol binding protein 1, cellular; CST6, cystatin E/M; CXCL, chemokine (C-X-C motif) ligand; DAL, differentially expressed in adenocarcinoma of the lung; DAPK, death-associated protein kinase; DKK, dickkopf; DLC, deleted in liver cancer; ESR, estrogen receptor; FHIT, fragile histidine triad; FLCN, folliculin; GREM, gremlin; GSTP, glutathione s-transferase protein; HOXB, homeobox family B; IGFBP, insulin-like growth factor binding protein; JUP, junction plakoglobin (also called γ-catenin); KTN, keratin; LOXL, lysyl oxidase-like; LSAMP, limbic system-associated membrane protein; MDRI, multiple drug resistance gene; MGMT, O-6-methylguanine-DNA methyltransferase; MT1G, metallothionein 1G; p14ARF, cyclin-dependent kinase inhibitor 2A alternative reading frame; p16INK4, cyclin-dependent kinase inhibitor 2A; PDLIM4, pdz and lim domain protein 4; PML, promyelocytic leukemia; PTGS, prostaglandin-endoperoxide synthase; RARB, retinoic acid receptor beta; RASSF, RAS association domain family; ROBO, roundabout; RPRM, reprimo; SDHB, Succinate dehydrogenase B; SFRP, secreted frizzled related protein; SLIT2, slit homolog 2; SPINT2, serine peptidase inhibitor, Kunitz type, 2; TIMP, Tissue inhibitor of metalloproteases; UCHL, ubiquitin carboxyl-terminal esterase L1; VHL, von Hippel-Lindau tumor suppressor; WIF, Wnt inhibitory factor; XAF, XIAP associated factor.