{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T22:56:58Z","timestamp":1791673018223,"version":"4.3.4"},"reference-count":68,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,7,14]],"date-time":"2008-07-14T00:00:00Z","timestamp":1215993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Primary diffuse large B\u2010cell lymphomas of different immune\u2010privileged sites (IP\u2010DLBCLs) share many clinical and biological features, such as a relatively poor prognosis, preferential dissemination to other immune\u2010privileged sites, and deletion of the HLA region, which suggests that IP\u2010DLBCL represents a separate entity. To further investigate the nature of IP\u2010DLBCL, we investigated site\u2010specific genomic aberrations in 16 testicular, nine central nervous system (CNS), and 15 nodal DLBCLs using array CGH. We also determined minimal common regions of gain and loss. Using robust algorithms including multiple testing procedures and the ACE\u2010it script, which is specifically designed for this task, the array CGH data were combined with gene expression data to explore pathways deregulated by chromosomal aberrations. Loss of 6p21.32\u2013p25.3, including the <jats:italic>HLA<\/jats:italic> genes, was associated with both types of IP\u2010DLBCL, whereas gain of 2p16.1\u2013p25.3 was associated with nodal DLBCL. Gain of 12q15\u2013q21.1 and 12q24.32\u2013q24.33 was associated with CNS DLBCL and gain of 19q13.12\u2013q13.43 with testicular DLBCL. Analysis of candidate genes in site\u2010specific regions and minimal common regions revealed two major groups of genes: one involved in the immune response, including regulation of HLA expression, and the other involved in apoptosis, including the p53 pathway. Many of these genes were also involved in homozygous deletions or high\u2010level gains. The presence of both shared and site\u2010specific aberrations in CNS and testicular DLBCLs underlines the concept of IP\u2010DLBCL but also indicates that IP\u2010DLBCLs of the CNS and testis do not form a single entity. The observed aberrations emphasize the importance of the deregulation of anti\u2010tumour immune response and apoptosis pathways. Copyright \u00a9 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2399","type":"journal-article","created":{"date-parts":[[2008,7,14]],"date-time":"2008-07-14T10:26:21Z","timestamp":1216031181000},"page":"209-217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Genomic alterations and gene expression in primary diffuse large B\u2010cell lymphomas of immune\u2010privileged sites: the importance of apoptosis and immunomodulatory pathways"],"prefix":"10.1002","volume":"216","author":[{"given":"M","family":"Booman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Szuhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Rosenwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HC","family":"Kluin\u2010Nelemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"de Jong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Schuuring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PM","family":"Kluin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,8,26]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404449"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35000501"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012914"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1732008100"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1545"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200404000-00005"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1399"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0542"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63284-1"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.11.141"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(00)00385-3"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2033"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1024"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1699"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10093"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.10.3569"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2617"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1510"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10824"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30378"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10155"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl646"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti677"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl269"},{"key":"e_1_2_7_26_2","unstructured":"VosseSJ van WieringenWN. ACE\u2010it: Array CGH expression integration tool.http:\/\/zeus.cs.vu.nl\/programs\/acewww\/ACE\u2010it_manual.pdf.2007."},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-9-r60"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11421"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(20000101)88:1<154::AID-CNCR21>3.0.CO;2-T"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2003.12.003"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428190701200042"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-006-9165-6"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00192429"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-05-1576"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-0897"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404919"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02185-05"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.7.4086"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.1.234.413k22_234_240"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.10891"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2000.tb00244.x"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.3.1168"},{"key":"e_1_2_7_44_2","unstructured":"BaudisM. Progenetix\u2014database of cytogenetic abnormalities in cancer.http:\/\/www.progenetix.de[October 2007]."},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0001-2815.2004.00290.x"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.159.11.5192"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.11.1809"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1480007"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506884200"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210993200"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408320200"},{"key":"e_1_2_7_52_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062041"},{"key":"e_1_2_7_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509430103"},{"key":"e_1_2_7_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1159"},{"key":"e_1_2_7_55_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408678200"},{"key":"e_1_2_7_56_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.5.2661"},{"key":"e_1_2_7_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2006.00209.x"},{"key":"e_1_2_7_58_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-04-1359"},{"key":"e_1_2_7_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1046"},{"key":"e_1_2_7_60_2","first-page":"2339","article-title":"Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene","volume":"58","author":"Su GH","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_7_61_2","first-page":"4177","article-title":"Human mitogen\u2010activated protein kinase kinase 4 as a candidate tumor suppressor","volume":"57","author":"Teng DHF","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_7_62_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.11.025"},{"key":"e_1_2_7_63_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0456"},{"key":"e_1_2_7_64_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503070102"},{"key":"e_1_2_7_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20361"},{"key":"e_1_2_7_66_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702212200"},{"key":"e_1_2_7_67_2","doi-asserted-by":"publisher","DOI":"10.1385\/IR:35:1:151"},{"key":"e_1_2_7_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526347"},{"key":"e_1_2_7_69_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031074"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2399","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.2399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:57:46Z","timestamp":1761051466000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.2399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,26]]},"references-count":68,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,10]]}},"alternative-id":["10.1002\/path.2399"],"URL":"https:\/\/doi.org\/10.1002\/path.2399","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8,26]]},"assertion":[{"value":"2008-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-06-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-08-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}