PT  - JOURNAL ARTICLE
AU  - Hwajeong Lee
AU  - Kai Wang
AU  - Adrienne Johnson
AU  - David M Jones
AU  - Siraj M Ali
AU  - Julia A Elvin
AU  - Roman Yelensky
AU  - Doron Lipson
AU  - Vincent A Miller
AU  - Philip J Stephens
AU  - Milind Javle
AU  - Jeffrey S Ross
TI  - Comprehensive genomic profiling of extrahepatic cholangiocarcinoma reveals a long tail of therapeutic targets
AID  - 10.1136/jclinpath-2015-203394
DP  - 2016 May 01
TA  - Journal of Clinical Pathology
PG  - 403--408
VI  - 69
IP  - 5
4099  - http://jcp.bmj.com/content/69/5/403.short
4100  - http://jcp.bmj.com/content/69/5/403.full
SO  - J Clin Pathol2016 May 01; 69
AB  - 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.