{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:35:02Z","timestamp":1791423302020,"version":"4.3.3"},"reference-count":26,"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> Lamins support the nuclear envelope and provide anchorage sites for chromatin, but they are also involved in DNA synthesis, transcription, and apoptosis. Although the lack of expression of A-type lamins in lymphoma and leukemia has been reported, the mechanism was unknown. We investigated the possible role of CpG island hypermethylation in lamin A\/C silencing and its prognostic relevance. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> The promoter CpG island methylation status of the lamin A\/C gene, encoding the A-type lamins, was analyzed by bisulfite genomic sequencing and methylation-specific polymerase chain reaction in human cancer cell lines (n = 74; from 17 tumor types), and primary leukemias (n = 60) and lymphomas (n = 80). Lamin A\/C expression was determined by reverse-transcription polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Lamin A\/C promoter CpG island methylation was found in hematologic malignancies: seven (50%) of 14 leukemia- and five (42%) of 13 lymphoma cell lines. The presence of hypermethylation was associated with the loss of gene expression while a demethylating agent restored expression. In primary malignancies, lamin A\/C hypermethylation was present in 18% (nine of 50) of acute lymphoblastic leukemias and 34% (14 of 41) of nodal diffuse large B-cell lymphomas. The presence of lamin A\/C hypermethylation in nodal diffuse large B-cell lymphomas correlated strongly with a decrease in failure-free survival (Kaplan-Meier, P = .0001) and overall survival (Kaplan-Meier, P = .0005). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Epigenetic silencing of the lamin A\/C gene by CpG island promoter hypermethylation is responsible for the loss of expression of A-type lamins in leukemias and lymphomas. The finding that lamin A\/C hypermethylation is associated with poor outcome in diffuse large B-cell lymphomas suggests important clinical implications. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.11.650","type":"journal-article","created":{"date-parts":[[2005,5,3]],"date-time":"2005-05-03T00:16:39Z","timestamp":1115079399000},"page":"3940-3947","source":"Crossref","is-referenced-by-count":127,"title":["Inactivation of the <i>Lamin A\/C<\/i> Gene by CpG Island Promoter Hypermethylation in Hematologic Malignancies, and Its Association With Poor Survival in Nodal Diffuse Large B-Cell Lymphoma"],"prefix":"10.1200","volume":"23","author":[{"given":"Ruben","family":"Agrelo","sequence":"first","affiliation":[{"name":"From the Cancer Epigenetics and Lymphoma Laboratories, Molecular Pathology Program, Spanish National Cancer Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Setien","sequence":"additional","affiliation":[{"name":"From the Cancer Epigenetics and Lymphoma Laboratories, Molecular Pathology Program, Spanish National Cancer Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Espada","sequence":"additional","affiliation":[{"name":"From the Cancer Epigenetics and Lymphoma Laboratories, Molecular Pathology Program, Spanish National Cancer Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jesus","family":"Artiga","sequence":"additional","affiliation":[{"name":"From the Cancer Epigenetics and Lymphoma Laboratories, Molecular Pathology Program, Spanish National Cancer Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"From the Cancer Epigenetics and Lymphoma Laboratories, Molecular Pathology Program, Spanish National Cancer Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"P\u00e9rez-Rosado","sequence":"additional","affiliation":[{"name":"From the Cancer Epigenetics and Lymphoma Laboratories, Molecular Pathology Program, Spanish National Cancer Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"Sanchez-Aguilera","sequence":"additional","affiliation":[{"name":"From the Cancer Epigenetics and Lymphoma Laboratories, Molecular Pathology Program, Spanish National Cancer Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario F.","family":"Fraga","sequence":"additional","affiliation":[{"name":"From the Cancer Epigenetics and Lymphoma Laboratories, Molecular Pathology Program, Spanish National Cancer Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Angel","family":"Piris","sequence":"additional","affiliation":[{"name":"From the Cancer Epigenetics and Lymphoma Laboratories, Molecular Pathology Program, Spanish National Cancer Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manel","family":"Esteller","sequence":"additional","affiliation":[{"name":"From the Cancer Epigenetics and Lymphoma Laboratories, Molecular Pathology Program, Spanish National Cancer Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"BIB1","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.2000.4216"},{"key":"BIB2","doi-asserted-by":"crossref","unstructured":"Broers JL, Machiels BM, van Eys GJ, et al: Dynamics of the nuclear lamina as monitored by GFP-tagged A-type lamins. J Cell Sci 112:3463,1999-3475,","DOI":"10.1242\/jcs.112.20.3463"},{"key":"BIB3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.37.110801.142705"},{"key":"BIB4","doi-asserted-by":"publisher","DOI":"10.1038\/323560a0"},{"key":"BIB5","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.3.531"},{"key":"BIB6","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1104-1062"},{"key":"BIB7","doi-asserted-by":"publisher","DOI":"10.1002\/path.1655"},{"key":"BIB8","doi-asserted-by":"crossref","unstructured":"Rober RA, Weber K, Osborn M: Differential timing of nuclear lamin A\/C expression in the various organs of the mouse embryo and the young animal: A developmental study. Development 105:365,1989-378,","DOI":"10.1242\/dev.105.2.365"},{"key":"BIB9","doi-asserted-by":"publisher","DOI":"10.1007\/s004180050138"},{"key":"BIB10","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(90)90076-L"},{"key":"BIB11","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1997.3735"},{"key":"BIB12","doi-asserted-by":"publisher","DOI":"10.1038\/5947"},{"key":"BIB13","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205600"},{"key":"BIB14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023075"},{"key":"BIB15","unstructured":"Paz MF, Fraga MF, Avila S, et al: A systematic profile of DNA methylation in human cancer cell lines. Cancer Res 63:1114,2003-1121,"},{"key":"BIB16","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh298"},{"key":"BIB17","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63150-1"},{"key":"BIB18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9821"},{"key":"BIB19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404842200"},{"key":"BIB20","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.5.1361.1361"},{"key":"BIB21","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.11.3909"},{"key":"BIB22","doi-asserted-by":"publisher","DOI":"10.1038\/nm0102-68"},{"key":"BIB23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012914"},{"key":"BIB24","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-200409000-00004"},{"key":"BIB25","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/94.1.26"},{"key":"BIB26","doi-asserted-by":"publisher","DOI":"10.1097\/01.cco.0000147383.04709.10"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2005.11.650","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T21:02:33Z","timestamp":1653512553000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2005.11.650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,10]]},"references-count":26,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2005,6,10]]}},"alternative-id":["10.1200\/JCO.2005.11.650"],"URL":"https:\/\/doi.org\/10.1200\/jco.2005.11.650","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,6,10]]}}}