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Loss of\n                    <jats:italic>Reprimo<\/jats:italic>\n                    gene expression accompanied by its promoter methylation was identified in pancreatic and lung cancers. Our aim was to examine the methylation status of\n                    <jats:italic>Reprimo<\/jats:italic>\n                    in a broad range of cancers. We examined\n                    <jats:italic>Reprimo<\/jats:italic>\n                    expression by RT\u2010PCR and the DNA methylation status of the\n                    <jats:italic>Reprimo<\/jats:italic>\n                    promoter by MSP in 39 tumor cell lines. Loss or downregulation of\n                    <jats:italic>Reprimo<\/jats:italic>\n                    expression was frequent (62%), and we confirmed that transcriptional repression of\n                    <jats:italic>Reprimo<\/jats:italic>\n                    was caused by hypermethylation (overall concordance 92%). Treatment of expression\u2010negative cells with 5\u2010aza\u20102\u2032\u2010deoxycytidine restored\n                    <jats:italic>Reprimo<\/jats:italic>\n                    expression. We then examined aberrant methylation of\n                    <jats:italic>Reprimo<\/jats:italic>\n                    in 645 tumors representing 16 tumor types. Promoter methylation of\n                    <jats:italic>Reprimo<\/jats:italic>\n                    was found in 79% of gastric cancers, 62% of gallbladder cancers, 57% of lymphomas, 56% of colorectal cancers, 40% of esophageal adenocarcinomas, 37% of breast cancers and 31% of leukemias. Methylation frequencies in ovarian cancers, bladder cancers, cervical cancers, brain tumors, malignant mesotheliomas and pediatric tumors were lower (0\u201320%).\n                    <jats:italic>Reprimo<\/jats:italic>\n                    methylation was rarely detected in nonmalignant tissues (0\u201311%) except for gastric epithelia. While colorectal polyps were also frequently methylated (27%), chronic cholecystitis samples were infrequently methylated (4%). Furthermore, we failed to identify\n                    <jats:italic>Reprimo<\/jats:italic>\n                    mutation in colorectal and gastric cancer cell lines and 50 primary colorectal cancers. Aberrant methylation of\n                    <jats:italic>Reprimo<\/jats:italic>\n                    with loss of expression is a common event and may contribute to the pathogenesis of some types of human malignancy. \u00a9 2005 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ijc.20910","type":"journal-article","created":{"date-parts":[[2005,2,7]],"date-time":"2005-02-07T11:19:56Z","timestamp":1107775196000},"page":"503-510","source":"Crossref","is-referenced-by-count":52,"title":["Aberrant methylation of\n                    <i>Reprimo<\/i>\n                    in human malignancies"],"prefix":"10.1002","volume":"115","author":[{"given":"Takao","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisayuki","family":"Shigematsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayan","family":"Shivapurkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinyere","family":"Echebiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Stastny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena","family":"Augustus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chew\u2010Wun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio 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