{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:53:46Z","timestamp":1791903226016,"version":"4.3.4"},"reference-count":23,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5569","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2002,5,3]]},"abstract":"<jats:p>\n            Neurofibromatosis type 1 (NF1) is one of the most prevalent dominantly inherited genetic diseases of the nervous system. NF1 encodes a tumor suppressor whose functional loss results in the development of benign neurofibromas that can progress to malignancy. Neurofibromas are complex tumors composed of axonal processes, Schwann cells, fibroblasts, perineurial cells, and mast cells. Through use of a conditional (\n            <jats:italic>cre<\/jats:italic>\n            \/\n            <jats:italic>lox<\/jats:italic>\n            ) allele, we show that loss of NF1 in the Schwann cell lineage is sufficient to generate tumors. In addition, complete NF1-mediated tumorigenicity requires both a loss of NF1 in cells destined to become neoplastic as well as heterozygosity in non-neoplastic cells. The requirement for a permissive haploinsufficient environment to allow tumorigenesis may have therapeutic implications for NF1 and other familial cancers.\n          <\/jats:p>","DOI":"10.1126\/science.1068452","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:54:32Z","timestamp":1027763672000},"page":"920-922","source":"Crossref","is-referenced-by-count":569,"title":["Neurofibromas in NF1: Schwann Cell Origin and Role of Tumor Environment"],"prefix":"10.1126","volume":"296","author":[{"given":"Yuan","family":"Zhu","sequence":"first","affiliation":[{"name":"Center for Developmental Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pritam","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Center for Developmental Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Charnay","sequence":"additional","affiliation":[{"name":"Ecole Normale Superieure, 46 rue d'Ulm 75230, Paris, Cedex 05, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis K.","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390\u20139133, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis F.","family":"Parada","sequence":"additional","affiliation":[{"name":"Center for Developmental Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","unstructured":"V. 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Genet. 89, 23 (1999).","journal-title":"Am. J. Med. Genet."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3171\/jns.1991.74.2.0248","volume":"74","author":"Halliday A. L.","year":"1991","unstructured":"Halliday A. L., et al., J. Neurosurg. 74, 248 (1991).","journal-title":"J. Neurosurg."},{"key":"e_1_3_1_22_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1084\/jem.191.1.181","volume":"191","author":"Ingram D. A.","year":"2000","unstructured":"Ingram D. A., et al., J. Exp. Med. 191, 181 (2000).","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_23_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.genet.34.1.1","volume":"34","author":"Knudson A. G.","year":"2000","unstructured":"Knudson A. G., Annu. Rev. Genet. 34, 1 (2000).","journal-title":"Annu. Rev. Genet."},{"key":"e_1_3_1_24_2","unstructured":"We thank P. Houston and F. Guignard for technical assistance; E. Rushing for pathology consultation; L. Klesse and S. Kernie for critically reading the manuscript; members of the Parada lab for support; M. Sliwkowski for providing heregulin; and members of the National Neurofibromatosis Foundation Consortium for stimulating discussions. Supported by grants from the National Institute of Neurological Disorders and Stroke and Department of Defense (L.F.P.). Y.Z. is a recipient of Young Investigator Award from the National Neurofibromatosis Foundation."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1068452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T02:20:38Z","timestamp":1704853238000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1068452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,5,3]]},"references-count":23,"journal-issue":{"issue":"5569","published-print":{"date-parts":[[2002,5,3]]}},"alternative-id":["10.1126\/science.1068452"],"URL":"https:\/\/doi.org\/10.1126\/science.1068452","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,5,3]]}}}