{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:47:52Z","timestamp":1792705672540,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,6,14]],"date-time":"2011-06-14T00:00:00Z","timestamp":1308009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurofibromatosis 1 (NF1) is an autosomal dominant disease that predisposes individuals to developing benign neurofibromas. Some features and consequences of NF1 appear to result from partial deficiency of neurofibromin (Nfn), the <jats:italic>NF1<\/jats:italic> gene protein product, as a result of haploinsufficiency for the <jats:italic>NF1<\/jats:italic> gene. Other features and consequences of NF1 appear to involve total deficiency of Nfn, which arises as a result of either loss of function of the second <jats:italic>NF1<\/jats:italic> allele or excess degradation of Nfn produced by the second allele in a particular clone of cells. We used immunofluorescence to assess the presence of Nfn in putative Schwann cells (S100B<jats:sup>+<\/jats:sup>) and non\u2010Schwann cells (S100B<jats:sup>\u2212<\/jats:sup>) in 36 NF1\u2010derived benign neurofibromas classified histologically as diffuse or encapsulated. The S100B<jats:sup>+<\/jats:sup>\/Nfn<jats:sup>\u2212<\/jats:sup> cell population made up only 18% \u00b1 10% (mean \u00b1 standard deviation) of the neurofibroma cells in both the diffuse and encapsulated neurofibromas. The proportion of S100B<jats:sup>+<\/jats:sup>\/Nfn<jats:sup>+<\/jats:sup> cells was significantly higher and the proportion of S100B<jats:sup>\u2212<\/jats:sup>\/Nfn<jats:sup>\u2212<\/jats:sup> cells was significantly lower in diffuse neurofibromas than in encapsulated neurofibromas. We isolated S100B<jats:sup>+<\/jats:sup>\/Nfn<jats:sup>+<\/jats:sup>, S100B<jats:sup>+<\/jats:sup>\/Nfn<jats:sup>\u2212<\/jats:sup>, and S100B<jats:sup>\u2212<\/jats:sup>\/Nfn<jats:sup>+<\/jats:sup> cells by laser microdissection and, using X\u2010chromosome inactivation profiles, assessed clonality for each cell type. We showed that, although some neurofibromas include a subpopulation of S100B<jats:sup>+<\/jats:sup>\/Nfn<jats:sup>\u2212<\/jats:sup> cells consistent with clonal expansion of a Schwann cell progenitor that has lost function of both <jats:italic>NF1<\/jats:italic> alleles, other neurofibromas do not show evidence of monoclonal proliferation of Schwann cells. Our findings suggest that, although clonal loss of neurofibromin function is probably involved in the development of some NF1\u2010associated neurofibromas, other pathogenic processes also occur. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22654","type":"journal-article","created":{"date-parts":[[2011,6,15]],"date-time":"2011-06-15T09:22:46Z","timestamp":1308129766000},"page":"1451-1460","source":"Crossref","is-referenced-by-count":11,"title":["S100B and neurofibromin immunostaining and X\u2010inactivation patterns of laser\u2010microdissected cells indicate a multicellular origin of some NF1\u2010associated neurofibromas"],"prefix":"10.1002","volume":"89","author":[{"given":"Tracy","family":"Tucker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent M.","family":"Riccardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Fee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Sutcliffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Vielkind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Wechsler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Wolkenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Friedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,6,14]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"1229","article-title":"Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen\u2010receptor gene correlates with X chromosome inactivation","volume":"51","author":"Allen RC","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-200404000-00004"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5447.2172"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0995-90"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6645"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2003.09.001"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20353"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/302747"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197102112840604"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.01.006"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000190651.45384.8B"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.neo.7900249"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600309"},{"key":"e_1_2_6_15_1","first-page":"400","article-title":"Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions","volume":"59","author":"Henske EP","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0794-353"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.1.44"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199903)24:3<283::AID-GCC15>3.0.CO;2-K"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9018"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200565"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1314405"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20389"},{"key":"e_1_2_6_23_1","volume-title":"Human tumors: histology, diagnosis and technique. Kobernick SD, translator","author":"Masson P","year":"1970"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-419X(00)00026-3"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.05.009"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63992-2"},{"key":"e_1_2_6_27_1","first-page":"172","article-title":"National Institutes of Health Consensus Development Conference Statement: neurofibromatosis","volume":"1","author":"National Institutes of Health","year":"1988","journal-title":"Neurofibromatosis"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1086\/321972"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-194"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2264(200008)28:4<425::AID-GCC8>3.0.CO;2-E"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(01)01955-4"},{"key":"e_1_2_6_32_1","first-page":"18","volume-title":"Neurofibromatosis: phenotype, natural history and pathogenesis","author":"Riccardi VM","year":"1992"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.7.1059"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0996-110"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1086\/515504"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.20.3055"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001702200"},{"key":"e_1_2_6_38_1","first-page":"600","article-title":"The neurofibroma in von Recklinghausen neurofibromatosis has a unicellular origin","volume":"49","author":"Skuse GR","year":"1991","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.274"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-010-0240-y"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155411407340"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(03)00031-1"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10305"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-009-0178-0"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10272"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20646"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068452"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.22654","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.22654","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T06:35:19Z","timestamp":1697438119000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.22654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,14]]},"references-count":46,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1002\/jnr.22654"],"URL":"https:\/\/doi.org\/10.1002\/jnr.22654","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,14]]}}}