{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:06:55Z","timestamp":1791011215917,"version":"4.1.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,12,18]]},"abstract":"<jats:p>\n                    Chromosome 3 allele loss in preinvasive bronchial\n abnormalities and carcinogen-exposed, histologically normal\n bronchial epithelium indicates that it is an early, possibly the first,\n somatic genetic change in lung tumor development. Candidate tumor\n suppressor genes have been isolated from within distinct 3p regions\n implicated by heterozygous and homozygous allele loss. We have proposed\n that\n                    <jats:italic>DUTT1,<\/jats:italic>\n                    nested within homozygously deleted regions\n at 3p12\u201313, is the tumor suppressor gene that deletion-mapping and\n tumor suppression assays indicate is located in proximal 3p. The same\n gene,\n                    <jats:italic>ROBO1<\/jats:italic>\n                    (accession number\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"gen\" xlink:href=\"AF040990\">AF040990<\/jats:ext-link>\n                    ), was\n independently isolated as the human homologue of the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    gene,\n                    <jats:italic>Roundabout<\/jats:italic>\n                    . The gene,\n coding for a receptor with a domain structure of the neural-cell\n adhesion molecule family, is widely expressed and has been\n implicated in the guidance and migration of axons, myoblasts, and\n leukocytes in vertebrates. A deleted form of the gene, which mimics a\n naturally occurring, tumor-associated human homozygous deletion of exon\n 2 of\n                    <jats:italic>DUTT1<\/jats:italic>\n                    \/\n                    <jats:italic>ROBO1<\/jats:italic>\n                    , was introduced into\n the mouse germ line. Mice homozygous for this targeted mutation, which\n eliminates the first Ig domain of Dutt1\/Robo1, frequently die\n at birth of respiratory failure because of delayed lung maturation.\n Lungs from these mice have reduced air spaces and increased mesenchyme,\n features that are present some days before birth. Survivors acquire\n extensive bronchial epithelial abnormalities including hyperplasia,\n providing evidence of a functional relationship between a 3p gene and\n the development of bronchial abnormalities associated with early lung\n cancer.\n                  <\/jats:p>","DOI":"10.1073\/pnas.251407098","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"15062-15066","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":143,"title":["Inadequate lung development and bronchial hyperplasia in mice with a targeted deletion in the\n                    <i>Dutt1<\/i>\n                    \/\n                    <i>Robo1<\/i>\n                    gene"],"prefix":"10.1073","volume":"98","author":[{"given":"Jian","family":"Xian","sequence":"first","affiliation":[{"name":"Medical Research Council (MRC) Molecular Oncology Group,\r Department of Oncology, University of Cambridge, MRC Centre, and\r MRC Laboratory of Molecular Biology, Hills Road,\r Cambridge CB2 2QH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Clark","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Molecular Oncology Group,\r Department of Oncology, University of Cambridge, MRC Centre, and\r MRC Laboratory of Molecular Biology, Hills Road,\r Cambridge CB2 2QH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalyn","family":"Fordham","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Molecular Oncology Group,\r Department of Oncology, University of Cambridge, MRC Centre, and\r MRC Laboratory of Molecular Biology, Hills Road,\r Cambridge CB2 2QH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Pannell","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Molecular Oncology Group,\r Department of Oncology, University of Cambridge, MRC Centre, and\r MRC Laboratory of Molecular Biology, Hills Road,\r Cambridge CB2 2QH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence H.","family":"Rabbitts","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Molecular Oncology Group,\r Department of Oncology, University of Cambridge, MRC Centre, and\r MRC Laboratory of Molecular Biology, Hills Road,\r Cambridge CB2 2QH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela H.","family":"Rabbitts","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Molecular Oncology Group,\r Department of Oncology, University of Cambridge, MRC Centre, and\r MRC Laboratory of Molecular Biology, Hills Road,\r Cambridge CB2 2QH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,12,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90641-B"},{"key":"e_1_3_3_2_2","first-page":"1949","volume":"60","author":"Wistuba I I","year":"2000","unstructured":"I I Wistuba, C Behrens, A K Virmani, G Mele, S Milchgrub, L Girard, J W Fondon, H R Garner, B McKay, F Latif, et al. 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