Abstract 72P
Background
Intrahepatic cholangiocarcinoma (ICC) is a common malignancy accounting for 10% to 20% of newly diagnosed liver cancers. At present times, great success have been achieved on the clinical trials targeting IDH1 mutations and FGFR2 fusions. However, precise treatment options for ICC remain limited and further detailed molecular profiling should be studied. Here we described the mutational landscape with ICC in Chinese patients by next-generation sequencing (NGS) assay.
Methods
240 Chinese patients with ICC were enrolled in this study. Genomic profiling of DNA was performed on formalin-fixed paraffin-embedded tumor samples by NGS with 381 cancer-related genes panel. The somatic and germline mutation data were both obtained. Only the pathogenic mutations and likely pathogenic mutations in clinical significance were rolled into our analysis.
Results
In 240 ICC samples collected, 228 (95.0%) patients had at least one mutation classed as pathogenic or likely pathogenic. We identified 260 mutations, spanning 170 genes, with TP53, KRAS, ARID1A, CDKN2A and IDH1 being the most frequently mutated genes, occurring in 36.3%, 27.5%, 18.8%, 13.8% and 11.2%, respectively. There were 247 somatic mutations and 17 germline mutations were detected, with a median tumor mutation burden of 5.1 mutations/MB. Amongst all, the highest mutational prevalence fell in somatic mutations (60.0%), followed by copy number amplification (25.8%), copy number reduction (10.8%) and fusions (6.3%). Of the 224 specimens with somatic mutations, KRAS (26.7%), TP53 (20.0%) and ARID1A (12.5%) were frequently mutated. 4.5% patients harbored FGFR2 mutations, including three (1.3%) with single nucleotide variant and twelve (5.0%) with fusions. The main FGFR2 fusion type was FGFR2-BICC1. BCL2L11 (13.3%), BRCA1 (1.3%) and BRCA2 (0.8%) were the most frequently germline mutated genes.
Conclusions
Our study revealed the genetic landscape of ICC. The data will provide more potential targets on further clinical research and practice.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Peking University Cancer Hospital & Institute.
Funding
Has not received any funding.
Disclosure
D. Zhang, B. Zhang, X. Zhao, Y. Bai: Full/Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.