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What are the genetic driver/alteration in intrahepatic cholangiocarcinoma? 


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Intrahepatic cholangiocarcinoma (ICC) is characterized by multiple genetic driver alterations. The most recurrent driver mutations in ICC include TP53, KRAS, SMAD4, IDH1/2, FGFR2-fus, and BAP1. These mutations exhibit pair-wise co-occurrences or mutual exclusivities and can be grouped into three genetic clusters. Cluster 1 is characterized by the tripartite interaction of KRAS, TP53, and SMAD4 mutations and is associated with a large bile duct histological phenotype and poor prognosis. Cluster 2 is characterized by co-association of IDH/BAP1 or FGFR2-fus/BAP1 mutations and is associated with a small bile duct phenotype and better prognosis. Cluster 3 consists of mutation-free ICC cases with intermediate clinicopathological features. Additionally, S100P and KRT17 have been identified as biomarkers that can stratify Cluster 3 ICCs into two distinct subtypes based on their biological and clinical characteristics.

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The paper identifies seven recurrent driver mutations in intrahepatic cholangiocarcinoma: TP53, KRAS, SMAD4, IDH1/2, FGFR2-fus, and BAP1.
The paper identifies 12 significantly mutated genes and 5 focal copy number alteration regions in intrahepatic cholangiocarcinoma (iCCA).
The genetic driver alterations in intrahepatic cholangiocarcinoma include IDH1 R132C, KRAS, SMAD4, ERBB2 gain, MDM2 gain, CKDN2A loss, and TERT alterations.
The genetic driver alterations in intrahepatic cholangiocarcinoma (iCCA) include FGFR2 gene fusions, NTRK1 fusions, FGFR1 fusions, FGFR3 fusions, FGFR4 fusions, ROS1 mutations, MET mutations, ALK mutations, IDH1 mutations, BRAF mutations, FGFR2 mutations, FGFR3 mutations, IDH2 mutations, and EGFR mutations.

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