Table 4.
Putative pathogenic pathways in clear cell adenocarcinoma of urinary tract
| Case | Gene | Driver | Role | Pathway | Biologic function | Tumor |
|---|---|---|---|---|---|---|
| 1 | WBSCR27 | - | - | - | Methyltransferase | Colorectal ADC; malignant melanoma |
| 2 | APC2 | - | - | Wnt/β-catenin pathway | Cell proliferation, apoptosis epithelial-mesenchymal transition, invasion, metastasis | Thyroid PTC, malignant melanoma, colorectal ADC, bladder urothelial carcinoma; HCC |
| CSMD3 | - | TSG | - | Tumor mutation burden, tumor-promoting inflammation | Ovarian serous carcinoma; breast IDC; colorectal ADC; uterine endometrial carcinoma | |
| LAMC2 | - | - | PI3K/AKT/mTOR pathway | Cell junction organization; increase aggressiveness; focal adhesion; inflammatory response pathway | HCC; malignant melanoma; uterine endometrial carcinoma, lung ADC | |
| 3 | ZNF219 | - | - | Chromatin remodeling | Transcription factor | Colorectal ADC; thyroid PTC; malignant melanoma; stomach cancer; uterine endometrial carcinoma |
| KRAS | + | OG | MAPK signaling pathway; PI3K/AKT/mTOR pathway; RAS signaling pathway | Cell proliferation, differentiation and migration | Lung ADC; pancreas ADC; colorectal ADC; uterine endometrial carcinoma | |
| 4 | KEAP1 | - | TSG | Keap1-Nrf2 pathway | Detoxification or antioxidation | Lung ADC, SqCC; endometrial carcinoma; uterine carcinomsarcoma; tonsil SqCC; biliary tract ADC |
| SMARCA4 | - | TSG | Chromatin remodeling | Gene expression regulation | Lung ADC; colorectal ADC; uterine endometrial carcinoma; bladder urothelial carcinoma; breast IDC | |
| CACNA1D | - | OG | MAPK signaling pathway | Cell proliferation, differentiation and migration | Uterine endometrial carcinoma; malignant melanoma; stomach ADC; lung SqCC | |
| AMER1 | + | TSG | Wnt/β-catenin pathway | - | Lung cancer; malignant melanoma; uterine endometrial carcinoma; Wilms tumor | |
| PIK3R1 | + | TSG | PI3K/AKT/mTOR pathway; JAK/STAT pathway; RAS signaling pathway; Cell cycle pathway | Cell proliferation; apoptosis; protein synthesis; metabolism; cell cycle; apoptosis | Uterine endometrial carcinoma; colorectal ADC; breast IDC; glioblastoma; lung ADC | |
| TNK2 | - | . | ACK1 signaling | Cell proliferation; apoptosis | Prostate cancer, breast IDC, pancreas ADC | |
| 5 | PBRM1 | + | TSG | Chromatin remodeling | - | Renal cell carcinoma, clear cell type; lung ADC; colorectal ADC; breast IDC |
| ARID1A | + | TSG | Chromatin remodeling | Cell cycle progression; invasiveness; stemness; differentiation | Uterine endometrial carcinoma; lung ADC; colorectal ADC; bladder urothelial carcinoma; breast IDC | |
| NKD1 | - | - | Wnt/β-catenin pathway | Cell proliferation; cell adhesion and motility; cell cycle progression; invasiveness | HCC; head and neck SqCC | |
| ACVRL1 | + | - | TGF-beta receptor signaling pathway; PI3K/AKT/mTOR pathway; MAPK pathway | Angiogenesis; invasion; migration; cell proliferation and growth; cell-cell interaction and differentiation; epithelial-mesenchymal transition; invasion; dissemination to distant organ sites | Breast IDC | |
| CAPN2 | - | - | Integrin-mediated cell adhesion pathway | Cellular shape; mobility; cell cycle regulation | Breast IDC, uterine endometrial carcinoma; HCC | |
| CC2D1B | - | - | EGFR signaling; TLR4 signaling | Transcription factor; cell proliferation | Uterine endometrial carcinoma | |
| CHD4 | - | OG, TSG | Chromatin remodeling | Genome instability and mutations | Uterine endometrial cancer; brain diffuse glioma; lung ADC; colorectal ADC | |
| KMT2D | + | OG, TSG | Chromatin remodeling | - | Lung adenocarcinoma; colorectal ADC; bladder urothelial carcinoma; breast IDC; uterine endometrial carcinoma | |
| TCF12 | - | TSG | Transcriptional regulation; MAPK pathway | - | Extraskeletal myxoid chondrosarcoma; hepatocellular carcinoma |
ACK1, activated Cdc42-associated tyrosine kinase 1; ADC, adenocarcinoma; EGFR, epidermal growth factor receptors; HCC, hepatocellular carcinoma; IDC, invasive ductal carcinoma; JAK, Janus kinase; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; OG, oncogene; PI3K, phosphatidylinositol-3-kinase; PTC, papillary thyroid carcinoma; SqCC, squamous cell carcinoma; STAT, signal transducer and activator of transcription; TGF, transforming growth factor; TRL4, Toll-like receptor 4; TSG, tumor suppressor gene.