Table 2.
Characteristics of a TET2-AR cancer protein nexus
| Gene | Locus1 | Germline2 | Somatic3 | Epigenetics | Signaling Pathway | Notes |
|---|---|---|---|---|---|---|
| AR | Xq12 | Androgen insensitivity, 300068 | Prostate, stomach, lung | – | Androgen signaling | Single copy in males |
| BAP1 | 3p21 | Tumor Predisposition Syndrome, 614327 | Melanoma, kidney, mesothelioma, bladder | Deubiquitinates histone H2A K119ub and HCFC1 (chr. Xq28) | Ubiquitin signaling, BRCA DNA repair | Frequently deleted in ccRCC, cytoplasm to nucleus shuttle |
| CCND1/Cyclin D1 | 11q13 | VHLS, kidney and colon cancer; multiple myeloma risk; 168461 | Esophagus, breast, head and neck, bladder, lung | – | Integrates DNA damage, hormone, growth factor, and differentiation signals to regulate the cell cycle G1/S transition with CDK4 and Rb | Cytoplasm to nucleus shuttle |
| CREBBP/CBP | 16p13 | Rubinstein-Taybi Syndrome, 180849 | Breast, bladder, lung, colon, stomach, uterus | Acetylates histones, NCOA1, and FOXO1; bromodomain binds acetylated histone lysine | Oxygen sensing with HIF1A, cAMP-dependent transcription, others | Cytoplasm to nucleus shuttle; acetyl-CoA, zinc binding |
| EP300 | 22q13 | Rubinstein-Taybi Syndrome, 613684 | Bladder, colorectal, cervical, melanoma, lung | Acetylates histone H3 K122 and K27, ALX1 K131, SIRT2, and HDAC1; bromo- domain binds acetylated histone lysine | Oxygen sensing with HIF1A, cAMP- dependent transcription, others | Cytoplasm to nucleus shuttle; acetyl-CoA, zinc binding |
| KAT2B/PCAF | 3p24 | – | Breast, kidney, bladder, lung, stomach, melanoma | Acetylates histone H3 and H4, and PTEN; bromodomain binds acetylated histone lysine | Oxygen sensing with HIF1A, cAMP- dependent transcrip- tion, others | Deleted in >90% ccRCC; acetyl-CoA, zinc binding |
| KDM6A | Xp11 | Kabuki Syndrome, 300867 | Bladder, kidney, esophogus, lung, myeloid leukemia | Demethylates histone H3 K27me3/2; correlated with H3 K4me and H2Aub | Androgen signaling | Single copy in males; iron, zinc, ascorbate binding |
| NONO | Xq13 | Papillary kidney cancer, 300854 | Breast, prostate, lung, uterus, kidney | – | Androgen signaling, cAMP-dependent transcription, nuclear paraspeckles | Single copy in males; fusion gene with enhancer-binding TF, TFE3 (chr. Xp11) |
| OGT | Xq13 | – | Prostate, uterus, melanoma | Glycosylates histone H2B S112 and H4, AKT1, and EZH2; correlated with DNA hmC and histone H3 K27me3 | Insulin signaling, glycolysis, hexosamine biosynthesis | Cytoplasm to nucleus shuttle, single copy in males, cytotoxic mitochondrial isoform |
| TET2 | 4q24 | Prostate cancer risk gene | MPD, melanoma, colon, kidney, prostate | DNA 5-mC to hmC, fC, and caC; 2- oxoglutarate to succinate; correlated with H2B GlcNAc | Androgen signaling | O2, iron, zinc binding |
1
Chromosome location;
2
alterations associated with disease, OMIM #;
3
selected tissues from COSMIC and the cBioPortal. VHLS, von Hippel-Lindau Syndrome; MPD, myelo- proliferative disorders; mC, methylcytosine; hmC, hydroxymethylcytosine; fC, formylcytosine; caC, carboxylcytosine; GlcNAc, glycosylation; me, methylation; me2/3, di- and tri-methylation; ub, ubiquitin; ccRCC, clear cell kidney cancer; chr, chromosome; --, no data or unknown