Combined hepatocellular cholangiocarcinoma: A clinicopathological update

Table 1 Summary of the findings of studies having examined the molecular landscape of combined hepatocellular-cholangiocarcinoma

Ref.	Technology	Molecular features/conclusion
Fujii et al[30]	Loss of heterozygosity, polymerase chain reaction	4q, 17p, 8p, 16q; common clonal evolution
Cazals-Hatem et al[8]	Loss of heterozygosity, Genome wide allelotyping	TP53, chromosome instability
Coulouarn et al[26]	Genome-wide transcriptional analysis	TGFβ and Wnt/β-catenin; Stem/progenitor features
Fujimoto et al[31]	Whole genome sequencing	TERT/IDH1/2, KRAS; Closer to HCC if hepatitis background and to; CCA in absence of hepatitis
Moeini et al[21]	Whole exome sequencing	TP53, TERT, IDH1/2, Chromosomal instability, MYC, IGF2, mTOR, Stem/progenitor features
Chen et al[54]	Whole genome sequencing	IDH1/2; Stem/progenitor features
Sasaki et al[29]	Whole genome sequencing	KRAS, IDH1/2, ARID1A, TERT; Variable association of HCC and/or CCA mutations
Jeon et al[32]	Multiplexed polymerase chain reaction-based sequencing	TP53, PTEN, MET, c-MYC, CDK6, CTNNB1, CCND1; Clonal heterogeneity
Wang et al[11]	Whole exome sequencing	VCAN, ACVR21, FCGBP; Stemness nature, monoclonal origin, intratumoral heterogeneity
Liu et al[10]	Whole exome sequencing, RNAseq	TP53, CTNNB1
Joseph et al[27]	Capture-based next generation sequencing	TERT, TP53, cell cycle genes (CCND1, CCNE1, CDKN2A), receptor tyrosine kinase/Ras/PI3-kinase pathway genes (MET, ERBB2, KRAS, PTEN), chromatin regulators (ARID1A, ARID2) and Wnt pathway genes (CTNNB1, AXIN, APC)
Sasaki et al[33]	Direct sequence	TERT, ARID1A, PBRM1, ARID2, BAP1, p53, KRAS, IDH1/2; Cholangiocellular carcinoma is different from cHCC-CCA
Xue et al[25]	Whole genome sequencing	TP53, TERT, AXIN1, KMT2D; Monoclonal origin in combined and mixed type; Both mono- and multiclonal origins in the separate type