Lingling Guo1, Fuping Zhou1, Huiying Liu1, Xiaoxia Kou1, Hongjuan Zhang1, Xiaofeng Chen2, Jinrong Qiu1. 1. Department of Biological Therapy, Eastern Hepatobiliary Surgery Hospital Shanghai 201805, China. 2. Department of Oncology, Jiangsu Province People's Hospital and Nanjing Medical University First Affiliated Hospital Nanjing, Jiangsu, China.
Abstract
BACKGROUND: The incidence of biliary system cancer is higher in the Chinese population than in the West. The overall prognosis of gallbladder cancer and cholangiocarcinoma is poor, and the current treatment is limited. In order to explore the pathogenesis of biliary tract cancers and potential targeted therapies, we mapped the mutation landscape of biliary tract cancer in the Chinese population and analyzed the molecular mechanism related to prognosis. METHODS: A total of 59 formalin fixed paraffin-embedded (FFPE) tissue samples were obtained from patients with operable biliary tract cancer. We conducted targeted capture sequencing of 620 genes through high-throughput sequencing technology and analyzed the fusion information of 13 genes. RESULTS: Mutations were detected in 88% samples, and the most frequent mutation base was C>T. Genes with higher single nucleotide variations (SNV) and copy number variations (CNV) frequency are TP53, KRAS, ARID1A, VEGFA, cyclin family related genes and cyclin-dependent kinase genes. Actionable mutations were detected in 59.3% samples, and germline mutations were detected in 22% samples. Patients with KRAS mutations, VEGFA pathway mutations and higher tumor mutation burden (TMB) may have poor prognosis. CONCLUSIONS: We explored the mutation characteristics and prognostic mechanism of biliary tract cancers in the Chinese population. This study provides potential evidence for targeted therapy and immunotherapy of biliary tract cancers. AJTR
BACKGROUND: The incidence of biliary system cancer is higher in the Chinese population than in the West. The overall prognosis of gallbladder cancer and cholangiocarcinoma is poor, and the current treatment is limited. In order to explore the pathogenesis of biliary tract cancers and potential targeted therapies, we mapped the mutation landscape of biliary tract cancer in the Chinese population and analyzed the molecular mechanism related to prognosis. METHODS: A total of 59 formalin fixed paraffin-embedded (FFPE) tissue samples were obtained from patients with operable biliary tract cancer. We conducted targeted capture sequencing of 620 genes through high-throughput sequencing technology and analyzed the fusion information of 13 genes. RESULTS: Mutations were detected in 88% samples, and the most frequent mutation base was C>T. Genes with higher single nucleotide variations (SNV) and copy number variations (CNV) frequency are TP53, KRAS, ARID1A, VEGFA, cyclin family related genes and cyclin-dependent kinase genes. Actionable mutations were detected in 59.3% samples, and germline mutations were detected in 22% samples. Patients with KRAS mutations, VEGFA pathway mutations and higher tumor mutation burden (TMB) may have poor prognosis. CONCLUSIONS: We explored the mutation characteristics and prognostic mechanism of biliary tract cancers in the Chinese population. This study provides potential evidence for targeted therapy and immunotherapy of biliary tract cancers. AJTR
Authors: Milind Javle; Maeve Lowery; Rachna T Shroff; Karl Heinz Weiss; Christoph Springfeld; Mitesh J Borad; Ramesh K Ramanathan; Lipika Goyal; Saeed Sadeghi; Teresa Macarulla; Anthony El-Khoueiry; Robin Kate Kelley; Ivan Borbath; Su Pin Choo; Do-Youn Oh; Philip A Philip; Li-Tzong Chen; Thanyanan Reungwetwattana; Eric Van Cutsem; Kun-Huei Yeh; Kristen Ciombor; Richard S Finn; Anuradha Patel; Suman Sen; Dale Porter; Randi Isaacs; Andrew X Zhu; Ghassan K Abou-Alfa; Tanios Bekaii-Saab Journal: J Clin Oncol Date: 2017-11-28 Impact factor: 44.544
Authors: S M Lipkin; V Wang; D L Stoler; G R Anderson; I Kirsch; D Hadley; H T Lynch; F S Collins Journal: Hum Mutat Date: 2001-05 Impact factor: 4.878
Authors: Jude Canon; Karen Rex; Anne Y Saiki; Christopher Mohr; Keegan Cooke; Dhanashri Bagal; Kevin Gaida; Tyler Holt; Charles G Knutson; Neelima Koppada; Brian A Lanman; Jonathan Werner; Aaron S Rapaport; Tisha San Miguel; Roberto Ortiz; Tao Osgood; Ji-Rong Sun; Xiaochun Zhu; John D McCarter; Laurie P Volak; Brett E Houk; Marwan G Fakih; Bert H O'Neil; Timothy J Price; Gerald S Falchook; Jayesh Desai; James Kuo; Ramaswamy Govindan; David S Hong; Wenjun Ouyang; Haby Henary; Tara Arvedson; Victor J Cee; J Russell Lipford Journal: Nature Date: 2019-10-30 Impact factor: 49.962
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702