{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T14:49:03Z","timestamp":1764254943472,"version":"3.46.0"},"reference-count":70,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T00:00:00Z","timestamp":1591315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:p>\n                    Spitzoid neoplasms are a challenging group of cutaneous melanocytic proliferations. They are characterized by epithelioid and\/or spindle\u2010shaped melanocytes and classified as benign Spitz nevi (SN), atypical Spitz tumors (AST), or malignant Spitz tumors (MST). The intermediate AST category represents a diagnostically challenging group since on purely histopathological grounds, their benign or malignant character remains unpredictable. This results in uncertainties in patient treatment and prognosis. The molecular properties of Spitzoid lesions, especially their transcriptomic landscape, remain poorly understood, and genomic alterations in melanoma\u2010associated oncogenes are typically absent. The aim of this study was to characterize their transcriptome with digital mRNA expression profiling. Formalin\u2010fixed paraffin\u2010embedded samples (including 27 SN, 10 AST, and 14 MST) were analyzed using the NanoString nCounter PanCancer Pathways Panel. The number of significantly differentially expressed genes in SN vs. MST, SN vs. AST, and AST vs. MST was 68, 167, and 18, respectively. Gene set enrichment analysis revealed upregulation of pathways related to epithelial\u2013mesenchymal transition and immunomodulatory\u2010, angiogenesis\u2010, hormonal\u2010, and myogenesis\u2010associated processes in AST and MST. A molecular signature of SN vs. MST was discovered based on the top\u2010ranked most informative genes:\n                    <jats:italic>NRAS<\/jats:italic>\n                    ,\n                    <jats:italic>NF1<\/jats:italic>\n                    ,\n                    <jats:italic>BMP2<\/jats:italic>\n                    ,\n                    <jats:italic>EIF2B4<\/jats:italic>\n                    ,\n                    <jats:italic>IFNA17<\/jats:italic>\n                    , and\n                    <jats:italic>FZD9<\/jats:italic>\n                    . The AST samples showed intermediate levels of the identified signature. This implies that the gene signature can potentially be used to distinguish high\u2010grade from low\u2010grade AST with a larger study cohort in the future. This combined histopathological and transcriptomic methodology is promising for prospective diagnostics of Spitzoid neoplasms and patient management in dermatological oncology.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.12897","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T03:39:45Z","timestamp":1589945985000},"page":"1326-1341","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A digital mRNA expression signature to classify challenging Spitzoid melanocytic neoplasms"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8808-4952","authenticated-orcid":false,"given":"Lisa M.","family":"Hillen","sequence":"first","affiliation":[{"name":"Department of Pathology GROW\u2010School for Oncology and Developmental Biology Maastricht University Medical Center (MUMC+) Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milan S.","family":"Geybels","sequence":"additional","affiliation":[{"name":"Department of Epidemiology GROW School for Oncology and Developmental Biology Maastricht University Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivelina","family":"Spassova","sequence":"additional","affiliation":[{"name":"Department for Translational Skin Cancer Research (TSCR) German Cancer Consortium (DKTK) University Hospital Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen C.","family":"Becker","sequence":"additional","affiliation":[{"name":"Department for Translational Skin Cancer Research (TSCR) German Cancer Consortium (DKTK) University Hospital Essen Essen Germany"},{"name":"Deutsches Krebsforschungsinstitut (DKFZ) Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thilo","family":"Gambichler","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ruhr\u2010University Bochum Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjan","family":"Garmyn","sequence":"additional","affiliation":[{"name":"Laboratory of Dermatology Department of Oncology and Department of Dermatology University Hospitals Leuven University of Leuven KUL Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"zur Hausen","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW\u2010School for Oncology and Developmental Biology Maastricht University Medical Center (MUMC+) Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost","family":"van den Oord","sequence":"additional","affiliation":[{"name":"Department of Pathology University Hospitals of Leuven University of Leuven KUL Leuven Belgium"},{"name":"Laboratory Translational Cell and Tissue Research University of Leuven, KU Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Winnepenninckx","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW\u2010School for Oncology and Developmental Biology Maastricht University Medical Center (MUMC+) Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0b013e3181934218"},{"key":"e_1_2_11_3_1","first-page":"591","article-title":"Melanomas of childhood","volume":"24","author":"Spitz S","year":"1948","journal-title":"Am J Pathol"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-2197.1978.tb05798.x"},{"volume-title":"Classification of Skin Tumours","year":"2018","author":"WHO","key":"e_1_2_11_5_1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000372-200408000-00008"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70608-9"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181cf7fa0"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000084"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2017.05.003"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2015.12.007"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00344"},{"key":"e_1_2_11_13_1","first-page":"574","article-title":"Gene expression analysis differentiates melanomas from Spitz Nevi","volume":"17","author":"Jansen B","year":"2018","journal-title":"J Drugs Dermatol"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2016.37"},{"key":"e_1_2_11_15_1","first-page":"1","article-title":"Spitz melanoma is a distinct subset of spitzoid melanoma","volume":"1","author":"Raghavan SS","year":"2020","journal-title":"Mod Pathol"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000495"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gdata.2016.10.006"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.044"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks461"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.126"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4198"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12012"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3361"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2016.237"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0b013e3282f5271c"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0b013e31824d448c"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2011.00950.x"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0296-144"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5324.333"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12488"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09181.x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800653"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16881"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16991"},{"key":"e_1_2_11_37_1","first-page":"41","article-title":"A rare mutation in EIF2B4 gene in an epileptic child with vanishing white matter disease: a case report","volume":"26","author":"Gungor O","year":"2015","journal-title":"Genet Couns"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12554"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038264"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21535"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-6-70"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-07-0317"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0b013e32830ce7d7"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2008.0118"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01159.x"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.1.7"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.12.2444"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.3892"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2015.11.014"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31559-9"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2016.07.029"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31822d5ff8"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/cup.12014"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31828fc283"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2014.07.005"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2001.140504.x"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.3.465"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205658200"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.450107"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811902106"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20180511"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.304"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3419"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/18899"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27746"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000198"},{"key":"e_1_2_11_67_1","first-page":"866","article-title":"Eruptive widespread Spitz nevi: can pregnancy be a stimulating factor?","volume":"40","author":"Onsun N","year":"1999","journal-title":"J Am Acad Dermatol"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.126.9.1239"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.dad.0000185249.21805.d3"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197707)40:1<217::AID-CNCR2820400134>3.0.CO;2-2"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2012.04.019"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2F2211-5463.12897","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.12897","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/2211-5463.12897","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.12897","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T14:44:36Z","timestamp":1764254676000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.12897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,5]]},"references-count":70,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/2211-5463.12897"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.12897","archive":["Portico"],"relation":{},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"type":"print","value":"2211-5463"},{"type":"electronic","value":"2211-5463"}],"subject":[],"published":{"date-parts":[[2020,6,5]]},"assertion":[{"value":"2020-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}