Abstract 2194: Comparison of molecular profiling between Chinese cholangiocarcinoma and gallbladder cancer through next-generation sequencing

Abstract

Abstract Background: Recently, some researchers proposed that molecular targeted therapies is ready for “prime time” in biliary tract cancer. However, few large-scale research data specifically analyze and compare the molecular characteristics of biliary tumors in the Chinese population. Here, we aim to report difference of molecular profiling of biliary tract cancers between Chinese cholangiocarcinoma (CCA) and gallbladder cancer (GCC) through next-generation sequencing, and summarize percentage of main targetable genetic alterations for CCA and GBC. Methods: Totally 1439 tumor sample of Chinese patient with biliary tract cancer were consecutively collected in China from January 2018 to July 2020, 907 patients were CCA, 532 were GCC. Gene mutation, microsatellite instability (MSI) were detected through next generation sequencing (NGS) by 3D Medicines, a laboratory accredited by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). Results: The main mutational gene between CCA and GCC were compared, and results showed that the top ten gene mutation in CCA patients were TP53 (57.6%,522/907), KRAS (35.2%, 320/907), XRCC5 (27.7%, 251/907), CYP2D6 (26.8%,243/907), MDM2 (26.0%,236/907), MSH2 (25.7%,233/907), BLM/VEGFA (24.9%,226/907), POLD (24.7%,224/907), PRSS1 (23.6%,214/907), ATM (23.3%, 212/907). While top ten gene mutation in GCC group were TP53 (76.3%,406/532), MSH2 (43.0%,229/532), CYP2D6 (30.4%, 162/532), MDM2 (28.8%,153/532), VEGFA (27.6%,147/532), POLD1 (27.4%, 146/532), BLM (27.4%,146/532), ATM (25.6%,136/532), PRSS1 (25.2%,134/532), PRKDC (24.8%,132/532). In addition, percentage of the main targetable genetic alterations were also compared between CCA and GCC, such as IDH (5.7% vs 0.9%), FGFR (10.2% vs 10.7%), BRAF (5.1% vs 4.3%), PIK3CA (9.9% vs 14.8%), NTRK (7.4% vs 8.3%), ERBB2/3 (11.8% vs 24.8%), CDKN2A/2B(18.5% vs 23.9%), ARID1A(17.3% vs 17.7&), PTEN (10.3% vs 13.9%), MET (6.3% vs 7.3%), SMAD4 (14.6% vs 14.5%). Conclusion: Accurately understand the gene mutation characteristics of biliary tract tumors is required to make “Precision Medicine” a reality for the “majority” of patients diagnosed with biliary tract cancer. Chinese patients with CCA and GCC have different gene mutations, especially the proportion of mutant genes that are currently targetable. Therefore, different strategy should be performed for CCA and GCC patients. Citation Format: Chao Yu, Hushan Zhang, Jun Luo, Songling Zhao. Comparison of molecular profiling between Chinese cholangiocarcinoma and gallbladder cancer through next-generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2194.