{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:58:26Z","timestamp":1790542706180,"version":"4.1.0"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T00:00:00Z","timestamp":1444262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0139902","type":"journal-article","created":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T18:13:39Z","timestamp":1444328019000},"page":"e0139902","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Exclusive Association of p53 Mutation with Super-High Methylation of Tumor Suppressor Genes in the p53 Pathway in a Unique Gastric Cancer Phenotype"],"prefix":"10.1371","volume":"10","author":[{"given":"Mina","family":"Waraya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishi","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Ema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuya","family":"Katada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,10,8]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S1535-6108(02)00215-5","article-title":"Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma","volume":"2","author":"K Yamashita","year":"2002","journal-title":"Cancer Cell"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"5982","DOI":"10.1158\/0008-5472.CAN-04-0993","article-title":"Inverse correlation between cyclin A1 hypermethylation and p53 mutation in head and neck cancer identified by reversal of epigenetic silencing","volume":"64","author":"Y Tokumaru","year":"2004","journal-title":"Cancer Res"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"3409","DOI":"10.1158\/0008-5472.CAN-05-1608","article-title":"N-methyl-D-aspartate receptor type 2B is epigenetically inactivated and exhibits tumor-suppressive activity in human esophageal cancer","volume":"66","author":"MS Kim","year":"2006","journal-title":"Cancer Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"3921","DOI":"10.1158\/0008-5472.CAN-05-1511","article-title":"PGP9.5 methylation in diffuse-type gastric cancer","volume":"66","author":"K Yamashita","year":"2006","journal-title":"Cancer Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/1541-7786.MCR-07-0213","article-title":"HOP\/OB1\/NECC1 promoter DNA is frequently hypermethylated and involved in tumorigenic ability in esophageal squamous cell carcinoma","volume":"6","author":"K Yamashita","year":"2008","journal-title":"Mol Cancer Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"4963","DOI":"10.1158\/0008-5472.CAN-04-3923","article-title":"PGP9.5 promoter methylation is an independent prognostic factor for esophageal squamous cell carcinoma","volume":"65","author":"DL Mandelker","year":"2005","journal-title":"Cancer Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/ijc.23354","article-title":"The role of PGP9.5 as a tumor suppressor gene in human cancer","volume":"123","author":"Y Tokumaru","year":"2008","journal-title":"Int J Cancer"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1002\/ijc.22934","article-title":"Quantitative hypermethylation of NMDAR2B in human gastric cancer","volume":"121","author":"JW Liu","year":"2007","journal-title":"Int J Cancer"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1002\/ijc.22025","article-title":"Silencing of the UCHL1 gene in human colorectal and ovarian cancers","volume":"119","author":"E Okochi-Takada","year":"2006","journal-title":"Int J Cancer"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1158\/1055-9965.EPI-08-0192","article-title":"Aberrant promoter methylation of multiple genes during pathogenesis of bladder cancer","volume":"17","author":"M Brait","year":"2008","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.1158\/1055-9965.EPI-09-0405","article-title":"Methylation markers for CCNA1 and C13ORF18 are strongly associated with high-grade cervical intraepithelial neoplasia and cervical cancer in cervical scrapings","volume":"18","author":"N Yang","year":"2009","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/1471-2407-11-220","article-title":"Aberrant methylation of N-methyl-D-aspartate receptor type 2B (NMDAR2B) in non-small cell carcinoma","volume":"11","author":"H Tamura","year":"2011","journal-title":"BMC Cancer"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1002\/mc.20798","article-title":"Promoter methylation of cyclin A1 is associated with human papillomavirus 16 induced head and neck squamous cell carcinoma independently of p53 mutation","volume":"50","author":"D Weiss","year":"2011","journal-title":"Mol Carcinog"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1158\/1055-9965.EPI-11-0970","article-title":"Tumor suppressor function of PGP9.5 is associated with epigenetic regulation in prostate cancer\u2014novel predictor of biochemical recurrence after radical surgery","volume":"21","author":"Y Mitsui","year":"2012","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s00595-010-4370-5","article-title":"Genomic and epigenetic profiles of gastric cancer: potential diagnostic and therapeutic applications","volume":"41","author":"K Yamashita","year":"2011","journal-title":"Surg Today"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1038\/onc.2010.76","article-title":"Potential utility of HOP homeobox gene promoter methylation as a marker of tumor aggressiveness in gastric cancer","volume":"29","author":"A Ooki","year":"2010","journal-title":"Oncogene"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/hep.22343","article-title":"Epigenetic identification of ubiquitin carboxyl-terminal hydrolase L1 as a functional tumor suppressor and biomarker for hepatocellular carcinoma and other digestive tumors","volume":"48","author":"J Yu","year":"2008","journal-title":"Hepatology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"e29783","DOI":"10.1371\/journal.pone.0029783","article-title":"The ubiquitin peptidase UCHL1 induces G0\/G1 cell cycle arrest and apoptosis through stabilizing p53 and is frequently silenced in breast cancer","volume":"7","author":"T Xiang","year":"2012","journal-title":"PLoS One"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1158\/1078-0432.CCR-09-3178","article-title":"The tumor suppressor UCHL1 forms a complex with p53\/MDM2\/ARF to promote p53 signaling and is frequently silenced in nasopharyngeal carcinoma","volume":"16","author":"L Li","year":"2010","journal-title":"Clin Cancer Res"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.cell.2009.12.055","article-title":"DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage in stroke","volume":"140","author":"W Tu","year":"2010","journal-title":"Cell"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/35050500","article-title":"DAP kinase activates a p19ARF\/p53-mediated apoptotic checkpoint to suppress oncogenic transformation","volume":"3","author":"T Raveh","year":"2001","journal-title":"Nat Cell Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1007\/s00018-006-5521-5","article-title":"Cyclin A1 is a p53-induced gene that mediates apoptosis, G2\/M arrest, and mitotic catastrophe in renal, ovarian, and lung carcinoma cells","volume":"63","author":"A Rivera","year":"2006","journal-title":"Cell Mol Life Sci"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"347","DOI":"10.5858\/2001-125-0347-NMFSAO","article-title":"Novel method for simultaneous analysis of p53 and K-ras mutations and p53 protein expression in single histologic sections","volume":"125","author":"K Yamashita","year":"2001","journal-title":"Arch Pathol Lab Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1056\/NEJMoa072252","article-title":"Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine","volume":"357","author":"S Sakuramoto","year":"2007","journal-title":"N Engl J Med"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"4387","DOI":"10.1200\/JCO.2011.36.5908","article-title":"Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer","volume":"29","author":"M Sasako","year":"2011","journal-title":"J Clin Oncol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1002\/ijc.2910540509","article-title":"p53 mutation in gastric cancer: a genetic model for carcinogenesis is common to gastric and colorectal cancer","volume":"54","author":"S Uchino","year":"1993","journal-title":"Int J Cancer"},{"key":"ref27","first-page":"223","article-title":"p53 gene mutations and protein nuclear accumulation are early events in intestinal type gastric cancer but late events in diffuse type","volume":"4","author":"GN Ranzani","year":"1995","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/(SICI)1097-0215(19960621)69:3<200::AID-IJC9>3.0.CO;2-3","article-title":"p53 accumulation and mutation are prognostic indicators of poor survival in human gastric carcinoma","volume":"69","author":"BH Lim","year":"1996","journal-title":"Int J Cancer"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1023\/A:1013275706401","article-title":"p53 mutation pattern and expression of c-erbB2 and c-met in gastric cancer: relation to histological subtypes, <italic>Helicobacter pylori<\/italic> infection, and prognosis","volume":"47","author":"S Kubicka","year":"2002","journal-title":"Dig Dis Sci"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1136\/mp.56.5.286","article-title":"Alterations in p53 predict response to preoperative high dose chemotherapy in patients with gastric cancer","volume":"56","author":"F Bataille","year":"2003","journal-title":"Mol Pathol"},{"key":"ref31","first-page":"276","article-title":"Diffuse type advanced gastric cancer showing dismal prognosis is characterized by deeper invasion and emerging peritoneal cancer cell: the latest comparative study to intestinal advanced gastric cancer","volume":"56","author":"K Yamashita","year":"2009","journal-title":"Hepatogastroenterology"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s10120-013-0253-y","article-title":"Lymph node ratio is a critical prognostic predictor in gastric cancer treated with S-1 chemotherapy","volume":"17","author":"A Ema","year":"2014","journal-title":"Gastric Cancer"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2014.01.005","article-title":"Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation","volume":"156","author":"K Ohnishi","year":"2014","journal-title":"Cell"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"R115","DOI":"10.1186\/gb-2012-13-12-r115","article-title":"Whole-genome reconstruction and mutational signatures in gastric cancer","volume":"13","author":"N Nagarajan","year":"2012","journal-title":"Genome Biol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1126\/science.1145720","article-title":"The genomic landscapes of human breast and colorectal cancers","volume":"318","author":"LD Wood","year":"2007","journal-title":"Science"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1158\/1078-0432.CCR-05-2096","article-title":"High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk","volume":"12","author":"T Maekita","year":"2006","journal-title":"Clin Cancer Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1158\/0008-5472.CAN-09-2755","article-title":"Inflammatory processes triggered by <italic>Helicobacter pylori<\/italic> infection cause aberrant DNA methylation in gastric epithelial cells","volume":"70","author":"T Niwa","year":"2010","journal-title":"Cancer Res"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1053\/j.gastro.2012.07.009","article-title":"Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation","volume":"143","author":"T Chiba","year":"2012","journal-title":"Gastroenterology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1158\/1541-7786.MCR-13-0091","article-title":"DNA damage-inducible gene, reprimo functions as a tumor suppressor and is suppressed by promoter methylation in gastric cancer","volume":"11","author":"A Ooki","year":"2013","journal-title":"Mol Cancer Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e44951","DOI":"10.1371\/journal.pone.0044951","article-title":"Cysteine dioxygenase 1 is a tumor suppressor gene silenced by promoter methylation in multiple human cancers","volume":"7","author":"M Brait","year":"2012","journal-title":"PLoS One"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/humu.10180","article-title":"TP53 and gastric carcinoma: a review","volume":"21","author":"CM Fenoglio-Preiser","year":"2003","journal-title":"Hum Mutat"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1053\/j.gastro.2003.08.033","article-title":"Meta-analysis of the relationship between cagA seropositivity and gastric cancer","volume":"125","author":"JQ Huang","year":"2003","journal-title":"Gastroenterology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nm1566","article-title":"<italic>Helicobacter pylori<\/italic> infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium","volume":"13","author":"Y Matsumoto","year":"2007","journal-title":"Nat Med"},{"key":"ref44","first-page":"511","article-title":"p53 alteration in gastric precancerous lesions","volume":"144","author":"YH Shiao","year":"1994","journal-title":"Am J Pathol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0139902","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,22]],"date-time":"2022-05-22T22:00:25Z","timestamp":1653256825000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0139902"}},"subtitle":[],"editor":[{"given":"Qian","family":"Tao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,10,8]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2015,10,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0139902","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,8]]}}}