Table 2.

Potential molecular alterations amenable for targeted therapies in iCCA

Gene or moleculeType of alterationNo. of positive/total samples (frequency)aReferences
Somatic mutations
 Metabolic enzymes
  IDH1/2Activating mutations143/951 (15%)(51–54, 56–62)
 Tyrosine kinase signaling
  KRASActivating mutations165/885 (19%)(50–53, 56–62)
  BRAFActivating mutations28/574 (5%)(50–51, 53–54, 55–59, 61)
  EGFRActivating mutations14/545 (3%)(50–51, 53–54, 55–59, 61)
 Chromatin-remodeling genes
  ARID1AInactivating mutations50/390 (13%)(51–54, 56–57, 59, 61–62)
  BAP1Inactivating mutations45/443 (11%)(51–54, 56–57, 59, 61–62)
  PBRM1Inactivating mutations34/443 (8%)(51–54, 56–57, 59, 61)
Tyrosine kinase (TK) fusion proteins
FGFR2 fusions
  FGFR2–BICC1TK fusion protein46/211 (22%)(51, 56, 57, 72, 73, 75)
  FGFR2–PPHLN1TK fusion protein17/153 (11%)(51, 56, 57, 72, 73, 75)
  FGFR2–AHCYL1TK fusion protein7/111 (6%)(51, 56, 57, 72, 73, 75)
  FGFR2–MGEA5TK fusion protein1/53 (2%)(51, 56, 57, 72, 73, 75)
  FGFR2–TACC3TK fusion protein2/53 (4%)(51, 56, 57, 72, 73, 75)
  FGFR2–KIAA1598TK fusion protein1/53 (2%)(51, 56, 57, 72, 73, 75)
ROS fusions
  ROS1 fusionsTK fusion protein2/23 (9%)(77)
Chromosomal aberrations
 11q13 (FGF19, CCND1, ORAOV1)High-level amplification5/128 (4%)(32)
  • aThe frequency in iCCA has been calculated by considering the number of samples presenting the molecular alteration over the total number of samples for which the specific alteration has been evaluated (discovery and validation set of samples) in different studies. Frequencies in iCCA have been calculated only in non–liver fluke cases.