Comprehensive genomic profiling of extrahepatic cholangiocarcinoma reveals a long tail of therapeutic targets.
OBJECTIVE
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.
Department of Pathology, Albany Medical College, Albany, New York, USA.
Hwajeong
H
Lee
Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
Kai
K
Wang
Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
Adrienne
A
Johnson
Department of Pathology, Albany Medical College, Albany, New York, USA.
David M
DM
Jones
Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
Siraj M
SM
Ali
Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
Julia A
JA
Elvin
Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
Roman
R
Yelensky
Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
Doron
D
Lipson
Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
Vincent A
VA
Miller
Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
Philip J
PJ
Stephens
The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Milind
M
Javle
Department of Pathology, Albany Medical College, Albany, New York, USA Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
Jeffrey S
JS
Ross
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D055815:Young Adult
BILIARY; HISTOPATHOLOGY; ONCOLOGY