{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:20:30Z","timestamp":1762176030011},"reference-count":28,"publisher":"American Association for Cancer Research (AACR)","issue":"19","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Deleted in colorectal cancer (DCC) is a candidate tumor-suppressor gene located at chromosome 18q21. However, DCC gene was found to have few somatic mutations and the heterozygous mice (DCC+\/\u2212) showed a similar frequency of tumor formation compared with the wild-type mice (DCC+\/+). Recently, DCC came back to the spotlight as a better understating of its function and relationship with its ligand (netrin-1) had shown that DCC may act as a conditional tumor-suppressor gene. We evaluated hypermethylation as a mechanism for DCC inactivation in head and neck squamous cell carcinoma (HNSCC). DCC promoter region hypermethylation was found in 75% of primary HNSCC. There was a significant correlation between DCC promoter region hypermethylation and DCC expression (assessed by immunohistochemistry; P = 0.021). DCC nonexpressing HNSCC cell lines JHU-O12 and JHU-O19 with baseline hypermethylation of the DCC promoter were treated with 5-aza-2\u2032-deoxycytidine (a demethylating agent) and reexpression of DCC was noted. Transfection of DCC into DCC-negative HNSCC cell lines resulted in complete abrogation of growth in all cell lines, whereas additional cotransfection of netrin-1 resulted in rescue of DCC-mediated growth inhibition. These results suggest that DCC is a putative conditional tumor-suppressor gene that is epigenetically inactivated by promoter hypermethylation in a majority of HNSCC. (Cancer Res 2006; 66(19): 9401-07)<\/jats:p>","DOI":"10.1158\/0008-5472.can-06-1073","type":"journal-article","created":{"date-parts":[[2006,10,3]],"date-time":"2006-10-03T15:44:22Z","timestamp":1159890262000},"page":"9401-9407","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["<i>Deleted in Colorectal Cancer<\/i> Is a Putative Conditional Tumor-Suppressor Gene Inactivated by Promoter Hypermethylation in Head and Neck Squamous Cell Carcinoma"],"prefix":"10.1158","volume":"66","author":[{"given":"Andre\u0301 Lopes","family":"Carvalho","sequence":"first","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Alice","family":"Chuang","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Wei-Wen","family":"Jiang","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Juna","family":"Lee","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Shahnaz","family":"Begum","sequence":"additional","affiliation":[{"name":"2Pathology, and"}]},{"given":"Luana","family":"Poeta","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Ming","family":"Zhao","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Carmen","family":"Jero\u0301nimo","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Chetan S.","family":"Nayak","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Hannah L.","family":"Park","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Mariana R.O.","family":"Brait","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Chunyan","family":"Liu","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Shaoyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Wayne","family":"Koch","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Vito Michele","family":"Fazio","sequence":"additional","affiliation":[{"name":"4Campus Bio-Medico University, Rome, Italy"}]},{"given":"Edward","family":"Ratovitski","sequence":"additional","affiliation":[{"name":"3Dermatology, Johns Hopkins Medical Institutions, Baltimore, Maryland; and"}]},{"given":"Barry","family":"Trink","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"William","family":"Westra","sequence":"additional","affiliation":[{"name":"2Pathology, and"}]},{"given":"David","family":"Sidransky","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Chul-so","family":"Moon","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]},{"given":"Joseph A.","family":"Califano","sequence":"additional","affiliation":[{"name":"1Otolaryngology-Head and Neck Surgery, Departments of"}]}],"member":"1086","published-online":{"date-parts":[[2006,10,3]]},"reference":[{"key":"2022061622275368000_B1","doi-asserted-by":"crossref","unstructured":"Fearon ER, Vogelstein B. 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