Feiling Feng1, Xiaobing Wu1, Xiaoliang Shi2, Qingxiang Gao1, Yue Wu1, Yong Yu1, Qingbao Cheng1, Bin Li1, Bin Yi1, Chen Liu1, Qing Hao2, Lin Zhang2, Chunfang Gao3, Xiaoqing Jiang4. 1. Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, People's Republic of China. 2. Origimed Co. Ltd, Shanghai, 201114, People's Republic of China. 3. Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, People's Republic of China. gaocf1115@163.com. 4. Department of Biliary Tract I, Eastern Hepatobiliary Surgery Hospital, No.225, Changhai Road, Yangpu District, Shanghai, 200433, People's Republic of China. Jxq1225@sina.com.
Abstract
BACKGROUND: Cholangiocarcinoma (CCA) is a rare malignant tumor of the biliary system. The heterogeneity of CCA leads to the lack of effective targeted treatment for CCA subtypes. The molecular characteristic of hilar CCA (hCCA) is still unclear. METHODS: A total of 63 hCCA patients were enrolled from Shanghai Eastern Hepatobiliary Surgery Hospital. Formalin-fixed, paraffin-embedded tumor tissues, and matched blood were collected and deep sequencing targeting 450 cancer genes were performed. Tumor mutation burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS: The most commonly mutated genes were TP53 (51.7%), NF1 and KRAS (20%, for both), SMAD4 (16.7%), FAT3 and FRS2 (13.3%, for both), NF1 (11.7%), and KMT2C, MDM2, and ATM (10%, for each) in hCCA. ARID1A, GATA6, and PREX2 mutations commonly occurred in female and KMT2C mutations mainly occurred in patients under 60 years old. Statistical analysis showed the association between ARID1A mutation and tumor stage (P = 0.041) and between NF1 mutation and high TMB (P = 0.0095). Furthermore, ARID1B mutation was identified to associate with the poor prognosis of Chinese hCCA patients (P = 0.004). CONCLUSION: The mutational characterization of hCCA is different from both extrahepatic CCA and intrahepatic CCA. ARID1B is a potential biomarker for prognosis prediction of Chinese hCCA patients.
BACKGROUND:Cholangiocarcinoma (CCA) is a rare malignant tumor of the biliary system. The heterogeneity of CCA leads to the lack of effective targeted treatment for CCA subtypes. The molecular characteristic of hilar CCA (hCCA) is still unclear. METHODS: A total of 63 hCCApatients were enrolled from Shanghai Eastern Hepatobiliary Surgery Hospital. Formalin-fixed, paraffin-embedded tumor tissues, and matched blood were collected and deep sequencing targeting 450 cancer genes were performed. Tumor mutation burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS: The most commonly mutated genes were TP53 (51.7%), NF1 and KRAS (20%, for both), SMAD4 (16.7%), FAT3 and FRS2 (13.3%, for both), NF1 (11.7%), and KMT2C, MDM2, and ATM (10%, for each) in hCCA. ARID1A, GATA6, and PREX2 mutations commonly occurred in female and KMT2C mutations mainly occurred in patients under 60 years old. Statistical analysis showed the association between ARID1A mutation and tumor stage (P = 0.041) and between NF1 mutation and high TMB (P = 0.0095). Furthermore, ARID1B mutation was identified to associate with the poor prognosis of Chinese hCCApatients (P = 0.004). CONCLUSION: The mutational characterization of hCCA is different from both extrahepatic CCA and intrahepatic CCA. ARID1B is a potential biomarker for prognosis prediction of Chinese hCCApatients.
Authors: W R Jarnagin; Y Fong; R P DeMatteo; M Gonen; E C Burke; J Bodniewicz BS; M Youssef BA; D Klimstra; L H Blumgart Journal: Ann Surg Date: 2001-10 Impact factor: 12.969
Authors: John D Hainsworth; Funda Meric-Bernstam; Charles Swanton; Herbert Hurwitz; David R Spigel; Christopher Sweeney; Howard Burris; Ron Bose; Bongin Yoo; Alisha Stein; Mary Beattie; Razelle Kurzrock Journal: J Clin Oncol Date: 2018-01-10 Impact factor: 44.544
Authors: Chaitanya R Churi; Rachna Shroff; Ying Wang; Asif Rashid; HyunSeon C Kang; Jacqueline Weatherly; Mingxin Zuo; Ralph Zinner; David Hong; Funda Meric-Bernstam; Filip Janku; Christopher H Crane; Lopa Mishra; Jean-Nicholas Vauthey; Robert A Wolff; Gordon Mills; Milind Javle Journal: PLoS One Date: 2014-12-23 Impact factor: 3.240