{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:25:14Z","timestamp":1791213914596,"version":"4.1.0"},"reference-count":56,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,6,10]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To analyze the occurrence of promoter hypermethylation in primary cutaneous T-cell lymphoma (CTCL) on a genome-wide scale, focusing on epigenetic alterations with pathogenetic significance. <\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p> DNA isolated from biopsy specimens of 28 patients with CTCL, including aggressive CTCL entities (transformed mycosis fungoides and CD30-negative large T-cell lymphoma) and an indolent entity (CD30-positive large T-cell lymphoma), were investigated. For genome-wide DNA methylation screening, differential methylation hybridization using CpG island microarrays was applied, which allows simultaneous detection of the methylation status of 8640 CpG islands. Bisulfite sequence analysis was applied for confirmation and detection of hypermethylation of eight selected tumor suppressor genes. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> The DNA methylation patterns of CTCLs emerging from differential methylation hybridization analysis included 35 CpG islands hypermethylated in at least four of the 28 studied CTCL samples when compared with benign T-cell samples. Hypermethylation of the putative tumor suppressor genes BCL7a (in 48% of CTCL samples), PTPRG (27%), and thrombospondin 4 (52%) was confirmed and demonstrated to be associated with transcriptional downregulation. BCL7a was hypermethylated at a higher frequency in aggressive (64%) than in indolent (14%) CTCL entities. In addition, the promoters of the selected tumor suppressor genes p73 (48%), p16 (33%), CHFR (19%), p15 (10%), and TMS1 (10%) were hypermethylated in CTCL. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Malignant T cells of patients with CTCL display widespread promoter hypermethylation associated with inactivation of several tumor suppressor genes involved in DNA repair, cell cycle, and apoptosis signaling pathways. In view of this, CTCL may be amenable to treatment with demethylating agents. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.11.353","type":"journal-article","created":{"date-parts":[[2005,5,17]],"date-time":"2005-05-17T00:35:24Z","timestamp":1116290124000},"page":"3886-3896","source":"Crossref","is-referenced-by-count":198,"title":["Epigenetic Profiling of Cutaneous T-Cell Lymphoma: Promoter Hypermethylation of Multiple Tumor Suppressor Genes Including <i>BCL7a<\/i>, <i>PTPRG<\/i>, and <i>p73<\/i>"],"prefix":"10.1200","volume":"23","author":[{"given":"Remco","family":"van Doorn","sequence":"first","affiliation":[{"name":"From the Departments of Dermatology and Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands; and Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem H.","family":"Zoutman","sequence":"additional","affiliation":[{"name":"From the Departments of Dermatology and Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands; and Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remco","family":"Dijkman","sequence":"additional","affiliation":[{"name":"From the Departments of Dermatology and Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands; and Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee X.","family":"de Menezes","sequence":"additional","affiliation":[{"name":"From the Departments of Dermatology and Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands; and Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzan","family":"Commandeur","sequence":"additional","affiliation":[{"name":"From the Departments of Dermatology and Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands; and Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aat A.","family":"Mulder","sequence":"additional","affiliation":[{"name":"From the Departments of Dermatology and Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands; and Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter A.","family":"van der Velden","sequence":"additional","affiliation":[{"name":"From the Departments of Dermatology and Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands; and Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten H.","family":"Vermeer","sequence":"additional","affiliation":[{"name":"From the Departments of Dermatology and Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands; 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Blood 95:2212,2000-2218,"},{"key":"BIB22","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.12.3653"},{"key":"BIB23","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/18.suppl_1.S96"},{"key":"BIB24","doi-asserted-by":"crossref","unstructured":"Benjamini Y, Hochberg Y: Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Statist Soc B 57:289,1995-300,","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"BIB25","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.9.2823"},{"key":"BIB26","unstructured":"Garcia-Manero G, Daniel J, Smith TL, et al: DNA methylation of multiple promoter-associated CpG islands in adult acute lymphocytic leukemia. Clin Cancer Res 8:2217,2002-2224,"},{"key":"BIB27","doi-asserted-by":"crossref","unstructured":"Kaltoft K, Bisballe S, Dyrberg T, et al: Establishment of two continuous T-cell strains from a single plaque of a patient with mycosis fungoides. 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Cancer Res 63:1789,2003-1797,"},{"key":"BIB33","doi-asserted-by":"publisher","DOI":"10.2144\/02333rv01"},{"key":"BIB34","unstructured":"Kawano S, Miller CW, Gombart AF, et al: Loss of p73 gene expression in leukemias\/lymphomas due to hypermethylation. Blood 94:1113,1999-1120,"},{"key":"BIB35","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/94.1.26"},{"key":"BIB36","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403216"},{"key":"BIB37","unstructured":"Conway KE, McConnell BB, Bowring CE, et al: TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers. 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