Table 2 Genetic mutations and polymorphisms associated with cholangiocarcinoma
Gene abbreviation | Gene name | Protein abbreviation | Protein name | Normal function(s)a |
|---|---|---|---|---|
Congenital mutations/polymorphisms | ||||
 ABCB4 | ATP Binding Cassette Subfamily B Member 4 | MDR3 | Multidrug resistance protein 3 | Transport of lipids from hepatocytes to bile |
 ABCB11 | ATP Binding Cassette Subfamily B Member 11 | BSEP | Bile Salt Exporter Pump | Transport of cholate conjugates from hepatocytes to bile |
 ABCC2 | ATP Binding Cassette Subfamily C Member 2 | MRP2 | Multidrug resistance-associated protein 2 | Transport of endogenous and xenobiotic compounds from hepatocytes to bile |
 ATP8B1 | ATPase Phospholipid Transporting 8B1 | FIC1 | Familial Intrahepatic Cholestasis type 1 | Transmembrane phospholipid transfer |
 COX-2 | Cyclooxygenase 2 | COX-2 | Cyclooxygenase 2 | Inflammatory cytokine |
 CYP1A2 | Cytochrome P450 1A2 | CYP1A2 | Cytochrome P450 1A2 | Xenobiotic metabolism |
 GST01 | Glutathione S-transferase omega-1 | GST01 | Glutathione S-transferase omega-1 | Detoxification of endogenous and xenobiotic compounds |
 KLRK1 | Killer Cell Lectin Like Receptor K1 | NKG2D | NKG2-D type II integral membrane protein | Tumour surveillance |
 MTHFR | Methylenetetrahydrofolate Reductase | MTHFR | 5,10-Methylenetetrahydrofolate reductase | DNA methylation |
 NAT2 | N-Acetyltransferase 2 | ARY2 | Arylamine N-acetyltransferase 2 | Drug and carcinogen metabolism |
 NR1H4 | Nuclear Receptor Subfamily 1 Group H Member 4 | BAR (FXR) | Bile acid receptor (Farnesoid X receptor) | Negative feedback inhibitor of bile acid synthesis |
 TYMS | Thymidylate Synthetase | TYMS | Thymidylate synthase | DNA repair |
 XRCC1 | X-Ray Repair Complementing Defective Repair In Chinese Hamster Cells 1 | XRCC1 | DNA repair protein XRCC1 | DNA repair |
Acquired mutations | ||||
 APC | Adenomatous polyposis coli | APC | Adenomatous polyposis coli | Tumour suppressor |
 ARID1A | AT-Rich Interaction Domain 1A | ARID1a | AT-rich interactive domain-containing protein 1A | Transcription factor |
 AXIN1 | AXIN1 | Axin-1 | Axis inhibitor protein 1 | Regulates apoptosis |
 BAP1 | BRCA1 Associated Protein 1 | BAP1 | Ubiquitin carboxyl-terminal hydrolase BAP1 | Regulates cell growth |
 BCL-2 | B cell Lymphoma-2 | Bcl-2 | B-cell lymphoma 2 | Regulates apoptosis |
 BCL2L1 | B Cell Lymphoma Like 1 | Bcl-xL b | B-cell lymphoma-extra large | Inhibits apoptosis |
Bcl-xS b | B-cell lymphoma-extra small | Promotes apoptosis | ||
 BRAF | B Rapidly Accelerated Fibrosarcoma | B-Raf | B-Rapidly Accelerated Fibrosarcoma | Proto-oncogene |
 BRCA1 | Breast Cancer 1 | BRCA1 | Breast cancer type 1 susceptibility protein | Tumour suppressor and DNA repair |
 BRCA2 | Breast Cancer 2 | BRCA2 | Breast cancer type 2 susceptibility protein | DNA repair |
 CCND1 | Cyclin D1 | CCND1 | G1/S-specific cyclin-D1 | Regulates cell growth |
 CDH1 | Cadherin 1 | E-cadherin | Epithelial cadherin | Tumour suppressor, cell adhesion |
 CDK6 | Cyclin-Dependent Kinase 6 | CDK6 | Cyclin-Dependent Kinase 6 | Controls cell cycle and differentiation |
 CDKN2A | Cyclin-Dependent Kinase Inhibitor 2A | p16 b | Protein 16 | Tumour suppressor |
p14arf b | Protein 14 Alternate Reading Frame | Tumour suppressor | ||
 CTNNB1 | Catenin Beta 1 | Β-catenin | Β-catenin | Proto-oncogene |
 EGFR (ERBB1) | Epidermal Growth Factor Receptor | EGFR (ErbB-1) | Epidermal Growth Factor Receptor | Proto-oncogene |
 ERBB2 (HER2) | Avian Erythroblastosis oncogene B2 | ErbB-2 (HER2) | Receptor tyrosine-protein kinase erbB-2 | Proto-oncogene |
 FBXW7 | F-Box And WD Repeat Domain Containing 7 | FBXW7 | F-box/WD repeat-containing protein 7 | Component of proteasomal protein degradation pathway |
 FGF19 | Fibroblast Growth Factor 19 | FGF19 | Fibroblast Growth Factor 19 | Regulation of bile salt synthesis |
 FGFR2 | Fibroblast Growth Factor Receptor 2 | FGFR2 | Fibroblast Growth Factor Receptor 2 | Cell surface receptor regulating cell proliferation, differentiation, migration and apoptosis |
 IDH1 | Isocitrate dehydrogenase 1 | Isocitrate de-hydrogenase 1 | Isocitrate dehydrogenase (cytoplasmic) | Glucose metabolism, indirectly mitigates oxidative stress |
 IDH2 | Isocitrate dehydrogenase 2 | Isocitrate de-hydrogenase 2 | Isocitrate dehydrogenase (mitochondrial) | Glucose metabolism, indirectly mitigates oxidative stress |
 Keap1 | Kelch-like ECH-associated protein 1 | KEAP1 | Kelch-like ECH-associated protein 1 | Prevents Nrf2-driven transcription |
 KRAS | Kirsten Rat Sarcoma | K-Ras | Kirsten Rat Sarcoma | Proto-oncogene |
 LTO1 | LTO1, ABCE1 maturation factor | LTO1 | Protein LTO1 homolog | Ribosome biogenesis |
 MCL-1 | Myeloid Cell Leukaemia 1 | Mcl-1 (3 isoforms) b | Induced myeloid leukaemia cell differentiation protein Mcl-1 | Isoform 1 resists apoptosis, isoforms 2 & 3 promote apoptosis |
 MDM2 | Mouse Double Minute 2 | Mdm2 | E3 ubiquitin-protein ligase Mdm2 | Proto-oncogene, p53 inhibitor |
 MYC | Avian myelocytomatosis virus oncogene cellular homolog | Myc | Myc proto-oncogene protein | Proto-oncogene |
 NF1 | Neurofibromin 1 | NF1 | Neurofibromin | Stimulates Ras activity |
 PBRM1 | Polybromo 1 | PBRM1 | Protein polybromo-1 | Negative regulator of cell proliferation |
 PIK3CA | Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha | PIK3CA | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform | Generates PIP3 that activates signalling cascades for cell growth, survival and motility |
 PRSS1 | Protease, Serine 1 | TRY1 | Trypsin-1 | Serine protease |
 PRSS2 | Protease, Serine 2 | TRY2 | Trypsin-2 | Serine protease |
 PTEN | Phosphatase And Tensin Homolog | PTEN | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN | Tumour suppressor |
 RAD51AP1 | RAD51 Associated Protein 1 | RAD51AP1 | RAD51 Associated Protein 1 | DNA damage repair |
 RASSF1A | Ras association domain family 1 isoform A | RASSF1A | Ras association domain-containing protein 1 isoform A | Tumour suppressor |
 ROS1 | Reactive Oxygen Species Proto-Oncogene 1, Receptor Tyrosine Kinase | ROS1 | Proto-oncogene tyrosine-protein kinase ROS | Epithelial cell differentiation, activation of signal pathways of cell differentiation, proliferation, growth and survival |
 SMAD4 | Small Mothers Against Decapentaplegic 4 | SMAD4 | Small Mothers Against Decapentaplegic 4 | Tumour suppressor, transcription factor |
 SOCS3 | Suppressor Of Cytokine Signaling 3 | SOCS3 | Suppressor Of Cytokine Signaling 3 | Signal transduction inhibitor |
 TP53 | Tumour Protein 53 | p53 | Protein 53 | Tumour suppressor |