Liang Xue1, Chao Guo2, Kang Zhang3, Hang Jiang4, Fei Pang5, Ying Dou5, Xiaoyan Liu5, Hanqing Lin5, Xiaowei Dong5, Songhui Zhao5, Ming Yao5, Kai Wang5, Yujie Feng6, Weiguang Gu7,8. 1. Department of Hepatobiliary & Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. 2. Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha 410005, China. 3. Department of Cancer, People's Hospital of Wuzhou, Wuzhou 543000, China. 4. Department of Hepato-Biliary-Pancreatic Surgery, The Third People's Hospital of Yunnan Province, Kunming 650011, China. 5. OrigiMed Inc., Shanghai 201114, China. 6. Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, China. 7. Department of Medical Oncology, People's Hospital of Nanhai District, Foshan 528200, China. 8. Department of Medical Oncology, Southern Medical University Nanfang Hospital, Guangzhou 510515, China.
Abstract
BACKGROUND: Cholangiocarcinoma (CCA) is a diverse group of malignancies arising from the intra- or extrahepatic biliary epithelium and characterized by its late diagnosis and fatal outcome. Extrahepatic cholangiocarcinoma (ECC) accounts for 90% of CCA. However, little is known about the comprehensive genomic alterations of ECC in Chinese population for providing clinical managements especially targeted therapy. METHODS: Comprehensive genomic profiling (CGP) was performed with next generation sequencing panel on paraffin-embedded tumor from a cohort of 80 Chinese ECC patients. RESULTS: The most frequently altered genes were TP53 (68%), KRAS (46%), SMAD4 (22%), ARID1A (20%) and CDKN2A (19%). Mutual exclusivity was observed between multiple genes including ARID1A:TP53, KRAS:LRP1B and NF2:TP53. Genetic alterations with potential therapeutic implications were identified in 43% of patients. The top three actionable alterations include CDKN2A (n=11), BRAF (n=5) and ERBB2 (n=4). Potentially actionable alterations were mainly enriched in the G1-S transition, homologous recombination repair, MAPK/ERK pathway. CONCLUSIONS: This is the largest data set of ECC cases providing a comprehensive view on genetic alterations in Chinese population which differs significantly from a US cohort, and indicates the potential clinical implications for targeted therapies. 2019 Hepatobiliary Surgery and Nutrition. All rights reserved.
BACKGROUND: Cholangiocarcinoma (CCA) is a diverse group of malignancies arising from the intra- or extrahepatic biliary epithelium and characterized by its late diagnosis and fatal outcome. Extrahepatic cholangiocarcinoma (ECC) accounts for 90% of CCA. However, little is known about the comprehensive genomic alterations of ECC in Chinese population for providing clinical managements especially targeted therapy. METHODS: Comprehensive genomic profiling (CGP) was performed with next generation sequencing panel on paraffin-embedded tumor from a cohort of 80 Chinese ECC patients. RESULTS: The most frequently altered genes were TP53 (68%), KRAS (46%), SMAD4 (22%), ARID1A (20%) and CDKN2A (19%). Mutual exclusivity was observed between multiple genes including ARID1A:TP53, KRAS:LRP1B and NF2:TP53. Genetic alterations with potential therapeutic implications were identified in 43% of patients. The top three actionable alterations include CDKN2A (n=11), BRAF (n=5) and ERBB2 (n=4). Potentially actionable alterations were mainly enriched in the G1-S transition, homologous recombination repair, MAPK/ERK pathway. CONCLUSIONS: This is the largest data set of ECC cases providing a comprehensive view on genetic alterations in Chinese population which differs significantly from a US cohort, and indicates the potential clinical implications for targeted therapies. 2019 Hepatobiliary Surgery and Nutrition. All rights reserved.
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