%0 Journal Article %T Somatic genetic aberrations in gallbladder cancer: comparison between Chinese and US patients %A Yang, Pingzhou %A Javle, Milind %A Pang, Fei %A Zhao, Wei %A Abdel-Wahab, Reham %A Chen, Xiaofeng %A Meric-Bernstam, Funda %A Chen, Huanwei %A Borad, Mitesh J. %A Liu, Yu %A Zou, Chuntao %A Mu, Shuo %A Xing, Yutong %A Wang, Kai %A Peng, Chuang %A Che, Xu %J Hepatobiliary Surgery and Nutrition %D 2019 %B 2019 %9 %! Somatic genetic aberrations in gallbladder cancer: comparison between Chinese and US patients %K %X Background: Gallbladder cancer (GBC) is often diagnosed at an advanced stage with limited therapeutic options and poor prognosis. The five-year survival rate of this cancer when diagnosed at an advanced stage is below 5%, and the median survival time is less than a year with standard gemcitabine-based chemotherapy. Survival benefit with second-line treatment is unknown. Thus, there is an urgent need for novel treatment strategies and targeted therapy based on next generation sequencing (NGS) may be of value. Methods: Comprehensive genomic profiling (CGP) was performed with NGS panel on paraffin-embedded tumors from a cohort of 108 Chinese and 107 US GBC patients. Clinical data were collected using an IRB approved protocol from a single-center in US and from China. Results: In Chinese and US GBC cohorts, an average of 6.4 vs . 3.8 genomic alterations (GAs) were identified per patient. The most frequent alterations were TP53 (69.4%), CDKN2A/B (26%), ERBB2 (18.5%), PIK3CA (17%) and CCNE1 (13%) in Chinese cohort, TP53 (58%), CDKN2A/B (25%), SMAD4 (17%), ARID1A (14%) and PIK3CA (14%) ERBB2 (13.1%) in US patients. NFE2L2 mutations were present in 6.5% of Chinese patients and not observed in the US cohort. Interestingly, ERBB2 genetic aberrations were significantly associated with better pathological tumor differentiation and tended to co-occurrence with CDKN2A/B mutations in both the Chinese and US GBC cases. Out of the top 9 dysregulated genetic pathways in cancer, Chinese patients harbored more frequent mutations in ERBB genes (30.6% vs . 19.0%, P=0.04). High frequency of PI3K/mTOR pathway variations was observed in both Chinese (37%) and US cohort (33%) (P=0.5). Additionally, both Chinese and US GBC patients exhibited a relatively high tumor mutational burden (TMB) (17.6% and 17.0%, respectively). In the Chinese cohort, a significant association was seen between direct repair gene alterations and TMB ≥10 muts/Mb (P=0.004). Conclusions: In our study, over 83% Chinese and 68% US GBC patients had actionable alterations that could potentially guide and influence personalized treatment options. The identification of high TMB, ERBB2 , CDKN2A/B , PI3K/mTOR pathway and DNA repair mutations indicated that both Chinese and US GBC patients may benefit from targeted or immune checkpoint inhibitors. %U https://hbsn.amegroups.org/article/view/25916 %V 8 %N 6 %P 604-614 %@ 2304-389X