title: Molecular profiling of intrahepatic and extrahepatic cholangiocarcinoma using next generation sequencing.
abstract: Cholangiocarcinoma is a heterogeneous malignant process, which is further classified into intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). The poor prognosis of the disease is partly due to the lack of understanding of the disease mechanism. Multiple gene alterations identified by various molecular techniques have been described recently. As a result, multiple targeted therapies for ICC and ECC are being developed. In this study, we identified and compared somatic mutations in ICC and ECC patients using next generation sequencing (NGS) (Ampliseq Cancer Hotspot Panel v2 and Ion Torrent 318v2 chips). Eleven of 16 samples passed internal quality control established for NGS testing. ICC cases (n=3) showed IDH1 (33.3%) and NRAS (33.3%) mutations. Meanwhile, TP53 (75%), KRAS (50%), and BRAF (12.5%) mutations were identified in ECC cases (n=8). Our study confirmed the molecular heterogeneity of ICC and ECC using NGS. This information will be important for individual patients as targeted therapies for ICC and ECC become available in the future.
authors.affiliation: Department of Pathology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, United States; Department of Medicine and Center for Genomic Medicine, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, United States.
authors.forename: Juan
authors.initials: J
authors.lastname: Putra
authors.affiliation: Department of Pathology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, United States; Department of Medicine and Center for Genomic Medicine, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, United States.
authors.forename: Francine B
authors.initials: FB
authors.lastname: de Abreu
authors.affiliation: Department of Pathology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, United States; Department of Medicine and Center for Genomic Medicine, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, United States.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Peterson
authors.affiliation: Department of Hematology and Oncology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
authors.forename: J Marc
authors.initials: JM
authors.lastname: Pipas
authors.affiliation: Department of Hematology and Oncology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
authors.forename: Kabir
authors.initials: K
authors.lastname: Mody
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Department of Pathology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, United States; Department of Medicine and Center for Genomic Medicine, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, United States. Electronic address: gregory.j.tsongalis@hitchcock.org.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsongalis
authors.affiliation: Department of Pathology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, United States; Department of Medicine and Center for Genomic Medicine, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, United States.
authors.forename: Arief A
authors.initials: AA
authors.lastname: Suriawinata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger
keywords: Extrahepatic cholangiocarcinoma; Intrahepatic cholangiocarcinoma; Next generation sequencing; Somatic mutations; Targeted therapy