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Somatic genetic aberrations in gallbladder cancer: comparison between Chinese and US patients

Hepatobiliary Surgery and Nutrition 2019年第6期8卷 604-614页

作者： Pingzhou Yang milind javle Fei Pang Wei Zhao Reham Abdel-Wahab Xiaofeng Chen Funda Meric-Bernstam Huanwei Chen Mitesh JBorad Yu Liu Chuntao Zou Shuo Mu Yutong Xing Kai Wang Chuang Peng Xu Che Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease Hunan Provincial People’s Hospital/The First Affiliated Hospital of Hunan Normal UniversityChangsha 410005China Department of Gastrointestinal Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA OrigiMed Inc. Shanghai 201114China Department of Hepatobiliary Surgery The Affiliated Hospital of Qingdao UniversityQingdao 266024China Department of Clinical Oncology Assiut University HospitalsAssiutEgypt Department of Oncology The Affiliated Hospital of Nanjing Medical UniversityNanjing 210000China Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer CenterHoustonTXUSA Department of Liver surgery First People’s Hospital of FoshanFoshan 528314China Division of Hematology and Oncology Mayo ClinicScottsdaleAZUSA Department of Pathology People’s Hospital of Hunan ProvinceChangsha 410005China National Cancer Center/National Clinical Research Center for Cancer/Department of Pancreatic and Gastric Surgery Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College/National Cancer Center/National Clinical Research Center for Cancer/Department of Hepatobiliary and Pancreatic SurgeryCancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116China

Background:Gallbladder cancer(GBC)is often diagnosed at an advanced stage with limited therapeutic options and poor *** 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 *** benefit with second-line treatment is ***,there is an urgent need for novel treatment strategies and targeted therapy based on next generation sequencing(NGS)may be of ***:Comprehensive genomic profiling(CGP)was performed with NGS panel on paraffin-embedded tumors from a cohort of 108 Chinese and 107 US GBC *** data were collected using an IRB approved protocol from a single-center in US and from ***:In Chinese and US GBC cohorts,an average of 6.4 vs.3.8 genomic alterations(GAs)were identified per *** most frequent alterations were TP53(69.4%),CDKN2A/B(26%),ERBB2(18.5%),PIK3CA(17%)and CCNE1(13%)in Chinese cohort,TP53(57.9%),CDKN2A/B(25%),SMAD4(17%),ARID1A(14%),PIK3CA(14%)and ERBB2(13.1%)in US ***2L2 mutations were present in 6.5%of Chinese patients and not observed in the US ***,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 *** 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 gu

关键词： Gallbladder cancer(GBC) comprehensive genomic profiling(CGP) ERBB2 CDKN2A/B PI3K/mTOR

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