Comprehensive genomic profiling of extrahepatic cholangiocarcinoma reveals a long tail of therapeutic targets

J Clin Pathol. 2016 May;69(5):403-8. doi: 10.1136/jclinpath-2015-203394. Epub 2015 Oct 23.

Abstract

Aim: We queried whether extrahepatic cholangiocarcinoma featured clinically relevant genomic alterations that could lead to targeted therapy.

Methods: Comprehensive genomic profiling by hybridisation capture of up to 315 genes was performed on 99 clinically advanced extrahepatic cholangiocarcinoma.

Results: There were 60 male and 39 female patients with a median age of 60.5 years. A total of 400 alterations were identified (mean 4.0; range 0-13) in 84 genes. Eighty-two (83%) of extrahepatic cholangiocarcinoma patients featured at least one clinically relevant genomic alterations including KRAS (43%); ERBB2 (9%), PTEN (7%); ATM and NF1 (6%) and CCND1, FBXW7, GNAS, MDM2 and NRAS (all at 5%). BRAF, BRCA2, CDK4, CDK6, FGFR1, FGFR3, PTCH1, RAF1 and STK11 were each altered in a single patient. No IDH1/2 mutations or FGFR2 gene fusions were identified.

Conclusions: Comprehensive genomic profiling of extrahepatic cholangiocarcinoma differs significantly from intrahepatic cholangiocarcinoma and pancreatic adenocarcinoma, and reveals diverse opportunities for the use of targeted therapies.

Keywords: BILIARY; HISTOPATHOLOGY; ONCOLOGY.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / pathology*
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / pathology
  • Female
  • Gene Expression Profiling*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation
  • Young Adult