Abstract 4349: Higher level of tumor mutational burden and 11q13 amplification in Chinese hepatocellular carcinoma patients

Introduction: The approval of immune checkpoint inhibitor (ICPI) for hepatocellular cancer (HCC) has changed the landscape of HCC treatment, which is the second most common and lethal malignancy in China. Several genomic features associated with ICPI efficacy in various types of cancers has been reported as potential predictive biomarkers. The application of comprehensive genomic profiling (CGP) on HCC might be useful in identifying ICPI responders or avoiding adverse effect. Experimental procedure: Comprehensive genomic profiling of 107 advanced HCC was performed on the FFPE tumor samples and matched blood by using a 450-gene next generation sequencing assay. The cohort of HCC patients comprises 86 males (median age = 56) and 21 females (median age = 52) whose gender disparity is in the normal range of HCC epidemiological statistic study from Asia-Pacific region. The ICPI therapy related genomic alterations such as tumor mutational burden (TMB) and 11q13 amplification were subsequently analyzed. Result: CGP revealed signature genomic alterations in HCC as previously reported but with exceptional higher frequency of TP53 mutations at 66.3% of the pts and relatively low rate of TERT variants at 32.7%. Higher level of TMB high values (>20 muts/Mb) was found in a significantly larger portion of the Chinese HCC patients (N=10, 9.3%), compared to only 1% in Western population (p-value 1.5E-05). The median TMB of the Chinese HCC cohort was 7.2 muts/Mb. In addition, 11q13 amplifications (FGF3, FGF4, FGF19 and CCND1) were detected in 6.5% of the Chinese HCC patients, which was associated with ICPI hyper-progression in a variety of cancers. The 7 patients with 11q13 amplifications had a median age of 65 yrs (range 52-78) which is significantly higher than the median age of the rest cohort at 55 yrs (range 28-79, p=0.02). The median TMB was 8 muts/Mb. Conclusion: Our preliminary results found that TMB high values were more commonly detected in Chinese HCC patients compared to Western population. It may indicate that more Chinese HCC patients could benefit from ICPI treatments. However, the high incidence of 11q13 amplifications related to hyper-progression response in the same cohort was observed. Therefore, the application of comprehensive genomic profiling companion diagnosis might be necessary in guiding the regimen and ICPI treatments. Citation Format: Xiaofeng Tang, Le Fan, Gang Chen, Weidong Guo, Fabo Qiu, Jun Wang, Jun Guo, Lijuan Chen, Peng Zhang, Weiwei Shi