Table 2.
Somatic mutations affecting TET genes in cancer
| Genes | Mutations in solid tumors | Mutations in hematological malignancies |
|---|---|---|
| TET genes | ||
| TET1 | Rare in endometrioid carcinomaa, colorectal carcinomas [105,137], lung [106,138,139] and bladder cancer [140] | Rare in AML [141] and CLL [142] |
| TET2 | Rare in endometrioid carcinomaa, colorectal carcinomas [105,137], melanoma and lung cancer [106,138,139] | Frequent in various cancers (see Table 3) |
| TET3 | Rare in endometrioid carcinoma and colorectal carcinomas [105,137] | Rare in CLL [142], PTCL [90] and T-ALL [143] |
| Epigenetic regulators of TET genes | ||
| Methyltransferases | ||
| DNMT1 | Rare in endometrioid carcinomaa, colorectal carcinomas [105,137], and lung cancer [106,138,139] | Rare in AML [141] |
| DNMT3A | Rare in endometrioid carcinomaa, colorectal carcinomas [105,137], lung cancer [106,138,139] and 2% in non-small cell lung cancer [144] | AML [128], MDS [145] and T-cell lymphomas [90,91] |
| Deaminase and glycosylase | ||
| AID | Rare in glioblastoma and medulloblastoma [146], endometrioid carcinomaa, colon cancer [105,137] and lung cancer [106,138,139] | T-ALL [147] |
| TDG | Rare in endometrioid carcinomaa, rare in glioblastomaa, colon cancer [104,136], lung [106,138,139] and thyroid cancer [148] | Not reported |
| Histone crosstalk regulators | ||
| OGT | Rare in endometrioid carcinomaa, colorectal carcinomas [105,137], lung cancer [106,138,139] and breast cancer [115,149] | DLBCL [150] and CLL [142] |
| IDAX | Rare in breast cancera, glioblastomaa, endometrioid carcinomaa, kidneya, colon cancer [105,137], lung cancer [106,138,139] and 1.2% in mouth and pharynx carcinoma [117] | Not reported |
| 5-mC and 5-hmC readers | ||
| MBD1 | Rare in endometrioid carcinomaa, colorectal carcinomas [105,137], lung cancer [106,138,139], breast cancer [149] and melanoma [109] | Rare in ALL [151] |
| MBD4 | Rare in endometrioid carcinomaa, colorectal carcinomas [105,137], lung cancer [106,138,139], breast cancer [115] and melanoma [109] | Rare in AML [141] |
| UHRF1 | Rare in endometrioid carcinomaa, colorectal carcinomas [105,137] and lung cancer [106,138,139] | Rare in B-ALL [152] |
| Other genes affecting TET functions | ||
| Metabolic enzymes | ||
| IDH1 | Rare in paragangliomas [153], frequent in chondrosarcomas [154], thyroid [155,156], prostate [157] and central nervous system cancers [102,158,159] | Frequent in AML [88], MDS [160], DLBCL [161] and B-ALL [162] |
| IDH2 | Rare in endometrioid carcinomaa and colorectal carcinomas [105,137], frequent in chondrosarcomas [154] and central nervous system cancers [102,158,159] | Frequent in AML [88], MDS [160] and AITL [89] |
| FH | Renal cell carcinoma [163] and paragangliomas [104] | Not reported |
| SDH | Renal cell carcinoma [164] and paragangliomas [104] | Not reported |
aCOSMIC database. Some mutations listed in this table have not been confirmed as somatic mutations. 5-mC, 5-methylcytosine; 5-hmC, 5-hydroxymethylcytosine; AID, activation-induced deaminase; AML, acute myeloid leukemia; AITL, angioimmunoblastic T-cell lymphoma; B-ALL, B-cell acute lymphoblastic leukemia; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; DNMT, DNA methyltransferase; FH, fumarate hydratase; IDAX, Inhibition of the Dvl and Axin complex; IDH, isocitrate dehydrogenase; MBD, methyl-binding domain; MDS, myelodysplastic syndrome; OGT, O-linked β-D-N acetylglucosamine transferase; PTCL, peripheral T-cell lymphoma; SDH, succinate dehydrogenase; T-ALL, T-cell acute lymphoblastic leukemia; TDG, thymine DNA glycosylase; TET, ten-eleven translocation; UHRF, ubiquitin-like with PHD and ring finger domains.