139827-158

Comprehensive genomic profiling of biliary tract cancers to reveal tumor-specific differences and genomic alterations.

Subcategory: 
Category: 
Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
General Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Welcome and General Session 4: Ordering Molecular Profiling for Patients: Are We Ready?
Abstract Number: 

231

Poster Board Number: 
General Poster Session B (Board #A2)
Citation: 
J Clin Oncol 33, 2015 (suppl 3; abstr 231)
Author(s): 
Jeffrey S. Ross, Kai Wang, Daniel Virgil Thomas Catenacci, Juliann Chmielecki, Siraj M. Ali, Julia Andrea Elvin, Roman Yelensky, Doron Lipson, Matthew J. Hawryluk, Vincent A. Miller, Philip J. Stephens, Milind M. Javle; Albany Medical College, Albany, NY; Foundation Medicine, Inc., Cambridge, MA; The University of Chicago, Chicago, IL; Foundation Medicine Inc., Cambridge, MA; The University of Texas MD Anderson Cancer Center, Houston, TX

Abstract Disclosures

Abstract: 

Background: Intrahepatic cholangiocarcinoma (IHCCA), extrahepatic cholangiocarcinoma (EHCCA) and gallbladder carcinomas (GBCA) typically present at an advanced stage and systemic chemotherapy provides only modest benefit in most cases. We queried whether comprehensive genomic profiling (GCP) of IHCCA, EHCCA and GBCA would reveal clinically relevant genomic alterations (CRGA) that could lead to targeted therapies. Methods: DNA was extracted from 40µ of FFPE sections from 412 IHCCA, 57 EHCCA and 85 GBCA. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of >600X for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. The CGP assay included base substitutions, INDELs, copy number alterations and fusions/rearrangements. CRGA were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: Patient characteristics were similar for all three tumor types. IHCCA and GBCa were more common in females and EHCCA were more common males. CGP revealed the results in the Table. Multiple antitumor responses to targeted therapies in each of the 3 tumor types will be presented. Conclusions: IHCCA, EHCCA and GBCA share GA in cell cycle regulation (CDKN2B) and chromatin remodeling (ARID1A). IHCCA features FGFR fusions, IDH1/2 substitutions, BRAF substitutions and MET amplification with a low KRAS mutation frequency. EHCCA and GBCA feature ERBB2 amplifications (GBCA > EHCCA) and PIK3CA/MTOR pathway alterations. EHCCA has a high KRAS mutation frequency whereas the KRAS GA in GBCA is low. The diverse landscape of CRGA in biliary tract cancers can serve as targets for therapies for patients with CCA, BDCA and GBCA and have the potential to improve outcomes for these aggressive forms of malignancy.

CGP findings.

IHCCAEHCCAGBCA
Total GA/patient2.94.44.0
CRGA/patient1.12.12.0
ERBB2 amplification3%11%16%
BRAF substitutions5%3%1%
KRAS substitutions22%42%11%
PI3KCA substitutions5%7%14%
FGFR1-3 fusions and amplifications11%03%
CDKN2A/B loss18%17%19%
IDH1/2 substitutions20%00
ARID1A alterations17%12%13%
MET amplification4%00