Table 2.
Germline (G) and somatic (S) mutations affecting coding (c) and non-coding (nc) regions of ABC genes in primary liver cancer
| Gene | Protein | Genetic mutations | G/S | Region | Protein mutations | Functional consequences | Clinical consequences | Studies | References |
|---|---|---|---|---|---|---|---|---|---|
| ABCB1 | MDR1 | c.1537A>T | S | c | Ile513Phe | Moderate | ND | TCGA-LIHC | TCGA |
| c.2621T>C | S | c | Val874Ala | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.20G>A | S | c | Arg7His | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.246delA | S | c | Gly83Efs*3 | High | ND | TCGA-LIHC | TCGA | ||
| c.466A>T | S | c | Met156Leu | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.1827A>T | S | c | Lys609Asn | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.28887T>G | S | c | Leu963Trp | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.590T>A | S | c | Met197Lys | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.3435C>T | S | c | Ile1145= | ND | Higher risk of HCC recurrence | HCC patients | [50] | ||
| ABCC1 | MRP1 | c.2512A>G | S | c | Ile838Val | Moderate | ND | TCGA-LIHC | TCGA |
| c.854C>A | S | c | Pro285Gln | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.2296G>A | S | c | Val766Met | Moderate | ND | TCGA-CHOL | TCGA | ||
| c.2281A>T | S | c | Ile761Phe | Moderate
Moderate |
ND | TCGA-LIHC | TCGA | ||
| c.2195T>A | S | c | Leu732Gln | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.-1666G>A | S | nc | Promoter | ND | Lower expression | HCC patients | [57] | ||
| c.-260G>C | S | nc | Promoter | ND | Higher expression | HepG2 and Hep3B cells | [58] | ||
| ABCC2 | MRP2 | c.3737T>A | S | c | Leu1246His | Moderate | ND | TCGA-LIHC | TCGA |
| c.71C>A | S | c | Pro24Gln | Moderate | ND | TCGA-CHOL | TCGA | ||
| c.1781G>A | S | c | Ser594Asn | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.2810A>G | S | c | Asn937Ser | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.715G>T | S | c | Val239Leu | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.1249G>A | S | c | Val471Ile | ND | Sorafenib efflux | HEK cells | [59] | ||
| c.3972C>T | S | c | Ile1324= | ND | Lower expression | Patients with CCA | [60] | ||
| c.-58A>C | S | nc | 5´ UTR | Modifier | ND | TCGA-LIHC | TCGA | ||
| c.-24C>T | S | nc | 5’ UTR | ND | Higher expression | Luciferase assay | [61] | ||
| ABCC3 | MRP3 | c.1666_1671dupTACGTG | S | c | Tyr556_Val557 | Moderate | ND | TCGA-LIHC | TCGA |
| c.614A>C | S | c | Asn205Thr | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.423G>T | S | c | Trp141Cys | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.422G>T | S | c | Trp141Leu | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.800C>A | S | c | Thr267Lys | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.1558G>A | S | c | Gly520Ser | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.2120A>G | S | c | Glu707Gly | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.1936A>C | S | c | Ser646Arg | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.-211C>T | S | nc | 5’ UTR | ND | Lower expression
Same expression |
Healthy liver | [62]
[63] |
||
| c.*179-9_*179-7delTCC | S | nc | Intron | Modifier | ND | TCGA-LIHC | TCGA | ||
| ABCC4 | MRP4 | c.1024C>A | S | c | Leu342Ile | Moderate | ND | TCGA-LIHC | TCGA |
| c.994G>A | S | c | Val332Met | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.382T>G | S | c | Ser128Ala | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.2174A>T | S | c | Gln725Leu | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.1037T>A | S | c | Ile346Asn | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.1785G>C | S | c | Gln595His | Moderate | ND | TCGA-LIHC | TCGA | ||
| ABCC5 | MRP5 | c.1745A>T | S | c | Asp582Val | Moderate | ND | TCGA-LIHC | TCGA |
| c.3724C>T | S | c | Arg1242Cys | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.4145T>C | S | c | Leu1382Phe | Moderate | ND | TCGA-LIHC | TCGA | ||
| ABCG2 | BCRP | c.34G>A | G | c | Val12Met | ND | Altered sorafenib pharmacokinetics | HCC patients | [43] |
| g.89078924T>C | G | c | Intron | ND | Altered sorafenib pharmacokinetics | HCC patients | [43] | ||
| c.734C>G | S | c | Phe245Arg | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.1500G>T | S | c | Lys500Asn | Moderate | ND | TCGA-CHOL | TCGA | ||
| c.745A>G | S | nc | Ile249Val | Moderate | ND | TCGA-LIHC | TCGA | ||
| g.89073197A>G | S | nc | Enhancer region | ND | Lower expression | HepG2 cells | [64] | ||
| g.88924371A>G | S | nc | Enhancer region | ND | Lower expression | HepG2 cells | [64] | ||
| g.89189602G>A | S | nc | Enhancer region | ND | Lower expression | HepG2 cells | [64] | ||
| ABCG2RE1*2 | S | nc | Enhancer region | ND | Lower expression | HepG2 cells | [64] | ||
| g.89026428A>C | S | nc | Enhancer region | ND | Higher expression | HepG2 cells | [64] |
Data obtained from referred literature and TCGA database. Functional consequences are based on VEP (Variant Effect Predictor; https://www.ensembl.org/vep) impact: High means that the variant is supposed to cause a high disruptive impact in the protein, which is likely to cause loss of function; Moderate means that the variant may be not disruptive, but results in a decrease effectiveness of the encoded protein; Modifier is usually referred to non-coding variants, whose impact is difficult to determine, although they can be involved in transcription or splicing changes. CCA: cholangiocarcinoma; HCC: hepatocellular carcinoma; ND: not described; TCGA: the cancer genome atlas; TCGA-LIHC: the cancer genome atlas - liver hepatocellular carcinoma; TCGA-CHOL: the cancer genome atlas - cholangiocarcinoma