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Please use this identifier to cite or link to this item: http://acervodigital.unesp.br/handle/11449/21494
Title: 
Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
Author(s): 
Institution: 
  • Universidade Estadual Paulista (UNESP)
  • Heliopolis Hosp
  • AC Camargo Canc Hosp
  • Oswaldo Cruz Hosp
  • Universidade de São Paulo (USP)
  • Faculdade de Medicina de São José do Rio Preto (FAMERP)
ISSN: 
1522-8002
Sponsorship: 
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Abstract: 
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, >= 3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.
Issue Date: 
1-Dec-2009
Citation: 
Neoplasia. Ann Arbor: Neoplasia Press, v. 11, n. 12, p. 1329-U100, 2009.
Time Duration: 
1329-U100
Publisher: 
Neoplasia Press
Source: 
http://www.neoplasia.com/abstract.php?msid=2814
URI: 
Access Rights: 
Acesso aberto
Type: 
outro
Source:
http://repositorio.unesp.br/handle/11449/21494
Appears in Collections:Artigos, TCCs, Teses e Dissertações da Unesp

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