Chun-Dong Zhang1,2, Hideyuki Takeshima1, Shigeki Sekine3, Satoshi Yamashita1, Yu-Yu Liu1, Naoko Hattori1, Hiroyuki Abe4, Hiroharu Yamashita2, Masahide Fukuda1, Yu Imamura5, Tetsuo Ushiku4, Hitoshi Katai6, Hiroshi Makino7, Masayuki Watanabe5, Yasuyuki Seto2, Toshikazu Ushijima8. 1. Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 2. Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan. 3. Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, 104-0045, Japan. 4. Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan. 5. Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan. 6. Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, 104-0045, Japan. 7. Department of Surgery, Tama-Nagayama Hospital, Nippon Medical School, Tokyo, 206-8512, Japan. 8. Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. tushijim@ncc.go.jp.
Abstract
BACKGROUND: Prediction of tissue origin of esophagogastric junction (EGJ) adenocarcinomas can be important for therapeutic decision, but no molecular marker is available. Here, we aimed to develop such a marker taking advantage of tissue-specific profiles of DNA methylation. METHODS: DNA methylation profiles of gastric adenocarcinomas (GACs) were obtained by an Infinium HumanMethylation450 BeadChip array, and those of esophageal adenocarcinoma (EACs) were obtained from the TCGA database. DNA from formalin-fixed paraffin-embedded (FFPE) samples was analyzed by bisulfite pyrosequencing. RESULTS: In the screening set, 51 of 145,841 CpG sites in CpG islands were methylated at significantly higher levels in 30 GACs compared to those in 30 EACs. Among them, SLC46A3 and cg09177106 were unmethylated in all the 30 EACs. Predictive powers of these two markers were successfully confirmed in an independent validation set (18 GACs and 18 EACs) (SLC46A3, sensitivity = 77.8%, specificity = 100%; cg09177106, sensitivity = 83.3%, specificity = 94.4%), and could be applied to FFPE samples (37 GACs and 18 EACs) (SLC46A3, P = 0.0001; cg09177106, P = 0.0028). On the other hand, EAC-specific markers informative in the FFPE samples could not be isolated. Using these GAC-specific markers, nine of 46 (19.6%) TCGA EGJ adenocarcinomas were predicted to be GACs. CONCLUSIONS: Two GAC-specific markers, SLC46A3 and cg09177106, had a high specificity for identifying the tissue origin of EGJ adenocarcinoma.
BACKGROUND: Prediction of tissue origin of esophagogastric junction (EGJ) adenocarcinomas can be important for therapeutic decision, but no molecular marker is available. Here, we aimed to develop such a marker taking advantage of tissue-specific profiles of DNA methylation. METHODS: DNA methylation profiles of gastric adenocarcinomas (GACs) were obtained by an Infinium HumanMethylation450 BeadChip array, and those of esophageal adenocarcinoma (EACs) were obtained from the TCGA database. DNA from formalin-fixed paraffin-embedded (FFPE) samples was analyzed by bisulfite pyrosequencing. RESULTS: In the screening set, 51 of 145,841 CpG sites in CpG islands were methylated at significantly higher levels in 30 GACs compared to those in 30 EACs. Among them, SLC46A3 and cg09177106 were unmethylated in all the 30 EACs. Predictive powers of these two markers were successfully confirmed in an independent validation set (18 GACs and 18 EACs) (SLC46A3, sensitivity = 77.8%, specificity = 100%; cg09177106, sensitivity = 83.3%, specificity = 94.4%), and could be applied to FFPE samples (37 GACs and 18 EACs) (SLC46A3, P = 0.0001; cg09177106, P = 0.0028). On the other hand, EAC-specific markers informative in the FFPE samples could not be isolated. Using these GAC-specific markers, nine of 46 (19.6%) TCGA EGJ adenocarcinomas were predicted to be GACs. CONCLUSIONS: Two GAC-specific markers, SLC46A3 and cg09177106, had a high specificity for identifying the tissue origin of EGJ adenocarcinoma.
Authors: Simone Giacopuzzi; Maria Bencivenga; Jacopo Weindelmayer; Giuseppe Verlato; Giovanni de Manzoni Journal: Gastric Cancer Date: 2016-12-30 Impact factor: 7.370
Authors: Manfred P Lutz; John R Zalcberg; Michel Ducreux; Antoine Adenis; William Allum; Daniela Aust; Fatima Carneiro; Heike I Grabsch; Pierre Laurent-Puig; Florian Lordick; Markus Möhler; Stefan Mönig; Radka Obermannova; Guillaume Piessen; Angela Riddell; Christoph Röcken; Franco Roviello; Paul Magnus Schneider; Stefan Seewald; Elizabeth Smyth; Eric van Cutsem; Marcel Verheij; Anna Dorothea Wagner; Florian Otto Journal: Eur J Cancer Date: 2019-03-15 Impact factor: 9.162
Authors: Jaffer A Ajani; Thomas A D'Amico; David J Bentrem; Joseph Chao; Carlos Corvera; Prajnan Das; Crystal S Denlinger; Peter C Enzinger; Paul Fanta; Farhood Farjah; Hans Gerdes; Michael Gibson; Robert E Glasgow; James A Hayman; Steven Hochwald; Wayne L Hofstetter; David H Ilson; Dawn Jaroszewski; Kimberly L Johung; Rajesh N Keswani; Lawrence R Kleinberg; Stephen Leong; Quan P Ly; Kristina A Matkowskyj; Michael McNamara; Mary F Mulcahy; Ravi K Paluri; Haeseong Park; Kyle A Perry; Jose Pimiento; George A Poultsides; Robert Roses; Vivian E Strong; Georgia Wiesner; Christopher G Willett; Cameron D Wright; Nicole R McMillian; Lenora A Pluchino Journal: J Natl Compr Canc Netw Date: 2019-07-01 Impact factor: 11.908