Table 2.
Subclassification of ICCs and their associated genetic alterations.
| Classification | Technology | Subtype I | Subtype II | References | ||
|---|---|---|---|---|---|---|
| Class | Characters | Class | Characters | |||
| Cells of origin | RNA-Seq WES Proteomics |
C1 class | - Mutations in TP53, BAP1, ARID1A, ARID2 - Altered expression of PLK1 and ECT2 |
C2 class | - Obesity - Bile acid metabolism - T-cell infiltration |
Chaisaingmongkol et al., 2017 |
| Anatomical structure | WGS WES RNA-Seq |
ICC-specific | - FGFR2 fusion - IDH1/2, EPHA2, BAP1 Mutation |
ICC and ECC shared | - KRAS, SMAD4, ARID1A and GNAS mutation | Nakamura et al., 2015 |
| Liver-fluke infection | Microarray | Liver fluke positive | - Xenobiotic metabolism | Liver fluke negative | - Growth factor signaling | Jinawath et al., 2006 |
| WGS WES WGS |
- TP53, KRAS, SMAD4, MLL3, ROBO2, RNF43, PEG3 and GNAS oncogene | - BAP1, IDH1/2 | Ong et al., 2012; Chan-On et al., 2013 | |||
| Epigenomics | - High somatic mutations - TP53, ARID1A and BRCA1/2 mutations - ERBB2 amplification - Hypermethylation in promoter CpG islands - H3K27me3-associated promoter mutations - Poorer prognosis |
- High copy-number alterations - BAP1 and IDH1/2 mutations - Altered PD-1/PD-L2 expression - Alterations and elevated expression of FGFR genes - Hypermethylation in promotor CpG shore - Better prognosis |
Jusakul et al., 2017 | |||
| Gene expression and copy number alterations | - Microarray - SNP array |
Proliferation class | - Oncogenic pathways - Mutations in KRAS, BRAF and EGFR - Chr11q13.2 amplification - Chr14q22.1 deletion - Moderate/poorly differentiated - Poorer prognosis |
Inflammation class | - Inflammatory pathways (Interleukins/chemokines), - STAT3 activation signaling pathway - Well differentiated - Better prognosis |
Sia et al., 2013a,b Sia et al., 2017 |
| Prognosis | - Microarray | Poor prognosis | - Mutations in KRAS and BRAF | Good prognosis | - No KRAS mutation | Andersen et al., 2013 |
| Mutations and copy number alterations | - WGS - RNA-seq |
M class | - Recurrent mutations of KRAS, TP53, IDH1 | C class | - Recurrent focal copy number alterations including deletions involving CDKN2A, ROBO1/2, RUNX3 and SMAD4 | Kim et al., 2016 |