Comprehensive Genomic Profiles of Patients With Biliary Tract Cancer

Biliary tract cancer (BTC) represents a heterogeneous disease with highly lethal malignancy and poor clinical outcomes. Here, we aimed to evaluate its genomic profiles to promote the development of precision medicine for BTC.

Genomic analysis of 134 BTC patients was performed by using targeted panel sequencing in this study. The results of genomic testing were analyzed by integrating patients' clinicopathologic data, including treatment information and clinical outcomes. The significance of genetic alterations in our cohort was compared with western BTCs by using public repositories NGS data from ICGC cohort.

The most frequent genomic alterations were TP53 (55.5%), KRAS (38.1%), ARID1A (17.2%), and CDKN2A (15.7%) in our cohort. Notably, Chinese BTC patients had a higher prevalence of TP53, KRAS, and LRP1B alterations compared with Western BTCs. Moreover, a higher frequency of IDH and FGFR2 alterations was found in intrahepatic cholangiocarcinoma (ICA), whereas BRIP1, KRAS, and POLE alterations were more likely to accumulate in extrahepatic cholangiocarcinoma (ECA), and those with gallbladder carcinoma (GBC) had a higher prevalence of NF1, MSH3, and PIK3R1 alterations. Furthermore, several genomic alterations were observed to have a significant impact on progression-free survival (PFS) and overall survival (OS) in our cohort. NGS data from the ICGC cohort further validated that TP53 was associated with inferior clinical outcomes both in Chinese and Western BTC patients, regardless of histopathologic subtypes or therapeutic approaches.

We demonstrated the real-world genomic characteristics of BTC patients, which may have promising implications for the development and application of precision medicine in the future. Well-designed prospective studies are mandatory to validate the predictive role of significant genomic alterations observed in our study.