Table 4.
Germline (G) and somatic (S) mutations affecting coding (c) and non-coding (nc) regions in genes coding phase II enzymes in primary liver cancer
| Gene | Protein | Genetic mutations | G/S | Region | Protein mutations | Functional consequences | Clinical consecuences | Studies | References |
|---|---|---|---|---|---|---|---|---|---|
| DCK | DCK | c.*823C>T | S | nc | 3’ UTR | Modifier | ND | TCGA-LIHC | TCGA |
| c.*157G>T | S | nc | 3’ UTR | Modifier | ND | TCGA-LIHC | TCGA | ||
| CDA | CDA | c.208G>A | G | c | Ala70Thr | High | Neutropenia and decreased clearance of gemcitabine | Several types of cancer | [87] |
| c.271A>G | S | c | Met91Val | Moderate | Neutral | TCGA-LIHC | TCGA | ||
| c.267-1G>A | S | c | Splice acceptor | High | Pathogenic | TCGA-LIHC | TCGA | ||
| c.157T>C | S | c | Cys53Arg | Moderate | ND | TCGA-LIHC | TCGA | ||
| MET | MET | c.65G>T | S | c | Ser22Ile | Moderate | ND | TCGA-LIHC | TCGA |
| c.3713A>T | S | c | His1238Leu | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.3767A>T | S | c | His1256Leu | Moderate | ND | TCGA-LIHC | TCGA | ||
| SULT1A1 | SULT1A1 | c.-265_-258delGTGAGGGG | S | nc | 5’ UTR | Modifier | ND | TCGA-CHOL | TCGA |
| c.-4-460_-4-453delGTGAGGGG | S | nc | Intron | Modifier | ND | TCGA-CHOL | TCGA | ||
| UGT2B7 | UGT2B7 | c.311C>A | S | c | Thr104Lys | Moderate | Neutral | TCGA-LIHC | TCGA |
| c.22G>T | S | c | Val8Leu | Moderate | ND | TCGA-LIHC | TCGA | ||
| c.282_283delTA | S | c | Lys95Glufs*26 | High | ND | TCGA-LIHC | TCGA | ||
| c.589_591delGTT | S | c | Val197del | Moderate | ND | TCGA-LIHC | TCGA | ||
| UGT1A1 | UGT1A1 | c.725T>A | S | c | Val242Glu | Moderate | ND | TCGA-LIHC | TCGA |
| UGT1A3 | UGT1A3 | c.779A>G | S | c | Asp260Gly | Moderate | ND | TCGA-LIHC | TCGA |
| c.457C>T | S | c | Pro153Ser | Modifier | ND | TCGA-LIHC | TCGA | ||
| c.867+13031C>T | S | c | Intron | Modifier | ND | TCGA-LIHC | TCGA | ||
| c.867+17971A>G | S | c | Intron | Moderate | ND | TCGA-LIHC | TCGA | ||
| UGT1A9 | UGT1A9 | c.668T>A | S | c | Phe223Tyr | Moderate | Neutral | TCGA-LIHC | TCGA |
Data obtained from TCGA database (https://cancergenome.nih.gov/) and referred literature. 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. ND: not described; TCGA: the cancer genome atlas; TCGA-LIHC: the cancer genome atlas - liver hepatocellular carcinoma; TCGA-CHOL: the cancer genome atlas - cholangiocarcinoma