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However, little is known about the methylation of known and putative TSGs in monoclonal gammopathies. Thus, the authors investigated the methylation frequencies of 10 genes in patients with monoclonal gammopathies.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The methylation patterns of the genes <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>INK4a<\/jats:italic><\/jats:sup> (<jats:italic>p16<\/jats:italic>), tissue inhibitor of metalloproteinase 3 (<jats:italic>TIMP3<\/jats:italic>), <jats:italic>p15<\/jats:italic><jats:sup><jats:italic>INK4b<\/jats:italic><\/jats:sup> (<jats:italic>p15<\/jats:italic>), E\u2010cadherin (<jats:italic>ECAD<\/jats:italic>), death\u2010associated protein kinase (<jats:italic>DAPK<\/jats:italic>), <jats:italic>p73<\/jats:italic>, RAS\u2010association domain family 1A (<jats:italic>RASSF1A<\/jats:italic>), <jats:italic>p14<\/jats:italic>, O<jats:sup>6<\/jats:sup>\u2010methylguanine DNA methyltransferase (<jats:italic>MGMT<\/jats:italic>), and retinoid acid receptor \u03b22 (<jats:italic>RAR\u03b2<\/jats:italic>) were determined in patients with monoclonal gammopathy of undetermined significance (MGUS; <jats:italic>n<\/jats:italic> = 29), smoldering multiple myeloma (SMM; <jats:italic>n<\/jats:italic> = 5), multiple myeloma (MM; <jats:italic>n<\/jats:italic> = 113), or plasma cell leukemia (PCL; <jats:italic>n<\/jats:italic> = 7) by methylation\u2010specific polymerase chain reaction analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Methylation frequencies for <jats:italic>p16<\/jats:italic>, <jats:italic>TIMP3<\/jats:italic>, <jats:italic>p15<\/jats:italic>, <jats:italic>ECAD<\/jats:italic>, <jats:italic>DAPK<\/jats:italic>, <jats:italic>p73<\/jats:italic>, <jats:italic>RASSF1A<\/jats:italic>, <jats:italic>p14<\/jats:italic>, <jats:italic>MGMT<\/jats:italic>, and <jats:italic>RAR\u03b2<\/jats:italic> were as follows: 28%, 35%, 10%, 0%, 17%, 21%, 14%, 14%, 7%, and 0%, respectively, in patients with MGUS and 36%, 29%, 27%, 27%, 22%, 15%, 15%, 9%, 4%, and 0%, respectively, in patients with MM. Methylation of at least 1 of these genes was detected in 79% of patients with MGUS and in 80% of patients with MM. Although methylation of <jats:italic>ECAD<\/jats:italic> was not detected in patients with MGUS, it was observed frequently in patients with MM and with even greater frequency in patients with PCL. It is noteworthy that an association was found between <jats:italic>ECAD<\/jats:italic> methylation and poor prognostic markers in patients with MM.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Methylation of certain genes can be detected frequently in patients with monoclonal gammopathies. The current data suggest that methylation of <jats:italic>ECAD<\/jats:italic> is a marker of disease progression in patients with MM and PCL. Cancer 2004. \u00a9 2004 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.20295","type":"journal-article","created":{"date-parts":[[2004,5,7]],"date-time":"2004-05-07T17:01:32Z","timestamp":1083949292000},"page":"2598-2606","source":"Crossref","is-referenced-by-count":61,"title":["DNA\u2010methylation analysis identifies the E\u2010cadherin gene as a potential marker of disease progression in patients with monoclonal gammopathies"],"prefix":"10.1002","volume":"100","author":[{"given":"Sonja","family":"Seidl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"Ackermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Keck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"N\u00f6sslinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph C.","family":"Zielinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Drach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Z\u00f6chbauer\u2010M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,6,2]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"1021","volume-title":"Hematology: basic principles and practice","author":"Kyle RA","year":"1999"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa01133202"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004320050011"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1996.d01-2939.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(03)01195-1"},{"key":"e_1_2_6_7_2","first-page":"56","article-title":"Prognostic factors in multiple myeloma","volume":"2","author":"Kyle RA","year":"1995","journal-title":"Stem Cells."},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.6.1925"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg816"},{"key":"e_1_2_6_10_2","first-page":"249","article-title":"Aberrant promoter methylation of multiple genes in non\u2010small cell lung cancers","volume":"61","author":"Z\u00f6chbauer\u2010M\u00fcller S","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_6_11_2","first-page":"3225","article-title":"A gene hypermethylation profile of human cancer","volume":"61","author":"Esteller M","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_6_12_2","first-page":"1835","article-title":"Hypermethylation of multiple genes in pancreatic adenocarcinoma","volume":"60","author":"Ueki T","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.9.2823"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401617"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.1.244"},{"key":"e_1_2_6_16_2","first-page":"1724","article-title":"Frequent death\u2010associated protein kinase promoter hypermethylation in multiple myeloma","volume":"7","author":"Ng MH","year":"2001","journal-title":"Clin Cancer Res."},{"key":"e_1_2_6_17_2","first-page":"2784","article-title":"SOCS\u20101, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma","volume":"27","author":"Galm O","year":"2002","journal-title":"Blood."},{"key":"e_1_2_6_18_2","unstructured":"GalmO JostE FabryU GehbauerG HermanJG OsiekaR.Aberrant methylation of the E\u2010cadherin 5\u2032 CpG island occurs with disease progression in multiple myeloma. 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