Table 2.
Summary of most relevant DNA/histone-modifying enzymes and chromatin remodeling complexes involved in testicular germ cell tumors according to The Cancer Genome Atlas (TCGA) database analysis.
| PLAYERS * | Most Frequently Deregulated (% of Cases) | Related Alterations (logOR) | SEvsNST | Best Performance (AUC) | Association with Stage | Survival Impact |
|---|---|---|---|---|---|---|
| DNA-modifying enzymes | ||||||
| DNMTs | DNMT3B (10) | DNMT3A and DNMT3B (co-occurrent, 2.785) | All ↓ in SE | DNMT3A (0.88) | Yes (DNMT3A/3B) | No |
| TETs | TET3 (8) | No | TET2 ↑ in SE | TET2 (0.79) | Yes (TET2) | No |
| Histone-modifying enzymes | ||||||
| ACETYLATION | ||||||
| KATs | ||||||
| MYST family | KAT6A (20) | KAT6A and KAT7 (mutually exclusive, <−3) |
KAT6A/6B ↑ in SE; KAT5/8 ↓ in SE |
KAT5 (0.75) | Yes (KAT6B and KAT8) | No |
| GNAT family | KAT9 (36) | KAT2A and KAT9 (mutually exclusive, <−3) |
KAT1/2A/2B/9 ↑ in SE; SLC33A1 and ATAT1 ↓ in SE |
KAT2A (0.78) | Yes (KAT2B) | No |
| Orphan family | KAT13C (41) |
KAT3B and KAT13C; KAT13A and KAT13C (co-occurrent, >3) |
KAT3B/13A/13C and CLOCK ↑ in SE | KAT13A (0.74) | Yes (KAT3B/13A/13C) | No |
| KDACs | ||||||
| HDACs | HDAC9 (14) | HDAC6 and HDAC8 (co-occurrent, 2.9) |
HDAC1/2/3/8/9/11 ↓ in SE; HDAC5/6/7 ↑ in SE |
HDAC11 (0.93) | Yes (HDAC1/11) | No |
| SIRTs | SIRT2/6 (10) | SIRT3 and SIRT6 (co-occurrent, >3) |
SIRT4 ↓ in SE; SIRT5 ↑ in SE |
SIRT4 (0.77) | Yes (SIRT4) | No |
| METHYLATION | ||||||
| KMTs | ||||||
| SET domain |
SETD4 (45) EZH2 (21) |
KMT2A and PRDM10; ASH1L and PRDM11; ASH1L and SMYD1 (co-occurrent, >3) |
KMT2B/2C/2D, SETD1A/D4/DB2, EZH1, SMYD3 and PRDM1/2/7/15 ↑ in SE; EHMT2, MECOM, SETD7, PRDM5 and EZH2 ↓ in SE |
EHMT2, PRDM1 and PRDM5 (AUC 0.96) | Yes (EHMT2, KMT2B and PRDM15) | Yes (KMT2D and PRDM2) |
| DOT1-like | DOT1L (9) | N/A | ↑ in SE | DOT1L (0.79) | No | No |
| PRMTs | PRMT8 (21) | No |
PRMT8 ↓ in SE PRMT9 ↑ in SE |
PRMT8 (0.83) | No | Yes (PRMT4) |
| KDMs | ||||||
| Jumonji-domain |
KDM5A (21) KDM7A (19) |
KDM4D and KDM4E (co-occurrent, >3) |
KDM2A/3A/3B/4D/7A/8, RIOX1 and HSPBAP1 ↑ in SE; TYW5 and JMJD8 ↓ in SE |
HSPBAP1 (0.93) | Yes (RIOX1 and KDM2A) | Yes (KDM6B and PHF2) |
| LSDs | LSD1 (8) | No | LSD2 ↑ in SE | LSD2 (0.73) | Yes (LSD2) | No |
| PHOSPHORYLATION | ||||||
| Kinases |
BAZ1B (34) PRKDC (33) |
CHEK2 and ATM (co-occurrent, 2.565) |
BAZ1B, ATM, ATR and RPS6KA5 ↑ in SE; RPS6KA4, PAK2 and AURKB ↓ in SE |
RPS6KA5 (0.89) | Yes (AURKB, ATM, ATR and RPS6KA4) | Yes (ATM, RPS6KA4 and PKN1) |
| UBIQUITINATION | ||||||
| Ubiquitin ligases | RING1 and RNF40 (10) | No |
RNF2 and BMI1 ↑ in SE; RING1, RNF20 and EBE2A ↓ in SE |
BMI1 (0.95) | Yes (BMI1, RNF2 and RNF20) | Yes (RNF40 and UBE2E1) |
| Deubiquitinating enzymes | USP16 and BAP1 (12) | No |
USP16 ↑ in SE; BAP1 ↓ in SE |
USP16 (0.89) | Yes (USP16) | No |
| Chromatin remodeling complexes | ||||||
| SWI/SNF | SMARCD1 (12) | ARID1B and PBRM1 (co-occurrent, >3) |
BRG1 and BRM ↑ in SE; SMARCD1 ↓ in SE |
BRM (0.84) | Yes (BRM) | No |
| ISWI | SNF2L (15) | SNF2L and BAZ1A (co-occurrent, 2.201) | SNF2L ↓ in SE | SNF2L (0.96) | Yes (SNF2L) | Yes (SNF2L) |
| CHD |
CHD7 (28) CHD4 (21) |
CHD3, CHD2 and CHD9 (co-occurrent alterations, >3) |
CHD1/2/6/7 ↑ in SE; CHD4 ↓ in SE |
CDH1 and CHD7 (0.81) | Yes (CHD7 and CHD8) | Yes (CHD2 and CHD8) |
| INO80 | ARP6 (12) | No | INO80 ↑ in SE | INO80 (0.88) | Yes (INO80) | Yes (SRCAP and RUVBL2) |
* Only the most relevant and significant players are represented. Upward (↑) and downward (↓) arrows stand for up- and downregulation, respectively. Abbreviations: AUC—area under the curve; N/A—not applicable; NST—non-seminomatous tumors; OR—odds ratio; SE—seminoma; TGCT—testicular germ cell tumors.