{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:01:04Z","timestamp":1782903664339,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,5,19]],"date-time":"2011-05-19T00:00:00Z","timestamp":1305763200000},"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":[[2011,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients carrying heterozygous germline truncating mutations in the <jats:italic>CYLD<\/jats:italic> gene develop multiple primary hair follicle\u2010related tumours. A highly patterned tumour, termed cylindroma, and a highly disorganized tumour, termed spiradenoma, may both develop in the same patient. Furthermore, histological features of both tumour types have been described within the same tumour specimen. We used three\u2010dimensional computer\u2010aided reconstruction of these tumours to demonstrate contiguous growth of cylindromas into spiradenomas, thus suggesting a transition between the two tumour types. To explore factors that may influence cutaneous tumour patterning, genome\u2010wide transcriptomic analysis of 32 CYLD\u2010defective tumours was performed. Overexpression of the Wnt\/\u03b2\u2010catenin signalling pathway was observed relative to normal perilesional tissue. Morphometric analysis was used to investigate the relationship between Wnt pathway\u2010related gene expression and tumour organization. This revealed an association between reduced Dickkopf 2 (DKK2\u2014a negative regulator of the Wnt\/\u03b2\u2010catenin signalling pathway) expression and loss of tumour patterning. Reduced DKK2 expression was associated with methylation of the <jats:italic>DKK2<\/jats:italic> gene promoter in the majority of tumour samples assayed. RNA interference\u2010mediated silencing of DKK2 expression in cylindroma primary cell cultures caused an increase in colony formation, cell viability, and anchorage\u2010independent growth. Using these data, we propose a model where epigenetic programming may influence tumour patterning in patients with <jats:italic>CYLD<\/jats:italic> mutations. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2896","type":"journal-article","created":{"date-parts":[[2011,3,14]],"date-time":"2011-03-14T10:18:42Z","timestamp":1300097922000},"page":"309-321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Transition from cylindroma to spiradenoma in CYLD\u2010defective tumours is associated with reduced DKK2 expression"],"prefix":"10.1002","volume":"224","author":[{"given":"Neil","family":"Rajan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Burn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Langtry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Sieber\u2010Blum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J","family":"Lord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Ashworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,5,19]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archdermatol.2009.262"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1827.1999.00890.x"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01811"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01802"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01803"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.12.018"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.190"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.056127"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062694"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603089103"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411049200"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.041"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1315"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2005.12.009"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708470200"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703268104"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.01.035"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/7747"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.20.4557"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.133"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.118.4.274"},{"key":"e_1_2_7_23_2","unstructured":"RasbandWS. ImageJ [Internet]. US National Institutes of Health Bethesda Maryland USA.1997\u20132009; Available from:http:\/\/rsb.info.nih.gov\/ij\/Accessed 1\/11\/2010."},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm178"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0558"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000372-198706000-00003"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2010.01100.x"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2316"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.01.034"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604259"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209439"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.05.042"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09560.x"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206854"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1130088"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010024"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80327-5"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.192"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09144.x"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2896","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2896","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.2896","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:10:27Z","timestamp":1761052227000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.2896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,19]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2011,7]]}},"alternative-id":["10.1002\/path.2896"],"URL":"https:\/\/doi.org\/10.1002\/path.2896","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,19]]},"assertion":[{"value":"2010-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-03-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}