Table 1.

Incidence of mutations in targetable pathways in CCAs included into the COSMIC database. iCCA, intrahepatic cholangiocarcinoma; eCCA, extrahepatic CCA.

Gene	%	Comment
EGFR	1.6	2.2–20% in other series [17,18,19,20,21]. Overexpression of EGFR and/or HER2/neu has been documented in 10–32% of iCCAs [17,18,19].
VEGF	0.7	VEGF overexpression has been reported in about 54% of iCCAs [19].
KRAS	23	More common in eCCAs [20,21].
NRAS	4	Similar distribution between iCCAs and eCCAs [20,21].
BRAF	4	There were no BRAF mutations in 137 eCCA cases reviewed by Walter et al. They were detected in 3.3% of 723 iCCAs [20,21].
FGFR2	2.1	FGFR2 fusions were observed in approximately 3–50% of iCCAS [22,23,24].
MET	0.7	MET has been found overexpressed in 12–58% of iCCAs [25,26].
ROS1	0.7	In other reports, the frequency of ROS1 alterations varies between 1.1% and 8.8% [27].
PIK3CA	7	Slightly more frequent in eCCAs in accordance with Walter et al. [21].
PTEN	3.3	Similar distribution between iCCAs and eCCAs [20,21].
IDH1	9	Rare in eCCAs [20,21].
IDH2	3	Not found in eCCAs [20,21].
JAK1/2, STAT3	0.6–1%	JAK/STAT signaling pathway activated in 50–70% of iCCAS [28].
ARID1A	13	Similar distribution between iCCAs and eCCAs [20,21].
PBRM1	6	More common in iCCAs [20,21].
BAP1	9	Rare in eCCAs [20,21].