Comprehensive molecular characterization of Chinese patients with biliary tract cancers.

Abstract

e16153 Background: Biliary tract cancers are clinically heterogenous with poor prognosis. The traditional location-based classification of biliary tract cancers is helpful while the boundary between subtypes is still ambiguous. We hereby analyzed the comprehensive molecular characterizations across different types among biliary tract cancers and further to identify the similarities and differences and help with the individualized treatment. Methods: Tumor tissue samples from 219 Chinese biliary tract cancer patients were profiled by next generation sequencing with a 539 gene panel by the Illumina NovaSeq 6000 (Illumina, San Diego, CA, USA) sequencing platform. Tumor mutation burden (TMB) was calculated by counting all nonsynonymous mutations per megabase of coding sequences. Results: A total of 219 biliary tract cancer (BTC) patients with a median age of 61 years(range 29–83 years) were enrolled, including 147 gallbladder cancer (GBC), 51 intrahepatic cholangiocarcinoma (iCCA) and 21 hilar cholangiocarcinoma (hCCA). These samples consisted of 93 males and 126 females. The most frequent mutated genes were TP53 (73%), ARID1A (18%), MUC16 (16%) in GBC, TP53 (57%), KRAS (35%), ARID1A (16%), PIK3CA (16%) in iCCA, TP53 (48%), KRAS (29%), ARID1A (14%) in hCCA. The mutation of BCORL1 (P = 0.002) and IRF4 (P = 0.006) had a significant association with age. The median TMB was 4.26 mutations/Mb in GBC, 2.94 mutations/Mb in iCCA and 2.84 mutations/Mb in hCCA. Patients with ATM mutation and FAT1 mutation had a significant higher TMB level (P＜0.001). The mutations of common target genes in different types of BTC were analyzed. The mutations of IDH1, target gene of Ivosidenib, were detected in 4 (1.83%) patients (1 in GBC, 2 in iCCA, 1in hCCA). The mutations of FGFR1/2/3/4, target gene of Erdafitinib, were detected in 10 (4.57%) patients (8 in GBC, 2 in iCCA, 0 in hCCA). The most frequently affected pathways in GBC, iCCA and hCCA were TP53 (78.2%, 60.8%, 47.6%), RTK-RAS (52.4%, 64.7%, 47.6%), PIK3 (34%, 39.2%, 33.3%). Conclusions: The genomic profiling and molecular characterization among different anatomic locations could support the exploration of tumor development mechanism and provide theoretic basis for developing diagnosis and treatment methods for biliary tract cancers patients.