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Mechanisms of Inactivation of PTCH1 Gene in Nevoid Basal Cell Carcinoma Syndrome: Modification of the Two-Hit Hypothesis
Pan, Shuang1,2,3; Dong, Qing1,2; Sun, Li-Sha1,2; Li, Tie-Jun1,2
刊名CLINICAL CANCER RESEARCH
2010-01-15
DOI10.1158/1078-0432.CCR-09-2574
16期:2页:442-450
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]HEDGEHOG SIGNALING PATHWAY ; TUMOR-SUPPRESSOR GENE ; ODONTOGENIC KERATOCYSTS ; GORLIN-SYNDROME ; DEVELOPMENTAL DEFECTS ; GERMLINE MUTATIONS ; HUMAN HOMOLOG ; PATCHED GENE ; DROSOPHILA ; CANCER
英文摘要

Purpose: PTCH1 has been identified as the gene responsible for nevoid basal cell carcinoma syndrome (NBCCS). Keratocystic odontogenic tumors (KCOT) are aggressive jaw lesions that may occur in isolation or in association with NBCCS. The aim of this study was to investigate the genetic and/or epigenetic mechanisms of inactivation of the PTCH1 gene in patients with NBCCS and related sporadic KCOTs.

Experimental Design: Loss of heterozygosity was analyzed in 44 patients (15 NBCCS-related and 29 sporadic KCOTs), all of whom were previously analyzed for PTCH1 mutations. Allelic location was established in tumors carrying two coincident mutations. PTCH1 mRNA expression and promoter methylation status were analyzed in a panel of KCOTs to define the possible role of epigenetic effects on PTCH1 inactivation.

Results: Although mutations and loss of heterozygosity of PTCH1 were frequently detected in both syndromic and nonsyndromic cases, hypermethylation of the PTCH1 promoter was not identified in the present series. Of all the 44 cases examined, 13 were identified to fit the two-hit model, 14 to conform to a one-hit model, and the remaining 17 cases showing no alteration in PTCH1. The distribution of two-hit, one-hit, and non-hit cases was significantly different between syndrome and nonsyndrome patients (P < 0.02).

Conclusions: This study indicates that PTCH1 gene alternation may play a significant role in the pathogenesis of NBCCS and the related sporadic tumors. Not only the standard two-hit model, but also haploinsufficiency or dominant-negative isoforms may be implicated in the inactivation of the PTCH1 gene. Clin Cancer Res; 16(2); 442-50. (C)2010 AACR.

语种英语
WOS记录号WOS:000278545000010
项目编号30625044 ; 30872900
资助机构National Nature Science Foundation of China
引用统计
被引频次:50[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55233
专题北京大学口腔医学院_口腔病理科
作者单位1.Peking Univ, Sch Stomatol, Dept Oral Pathol, Beijing 100081, Peoples R China
2.Peking Univ, Hosp Stomatol, Dept Oral Pathol, Beijing 100081, Peoples R China
3.Harbin Med Coll, Affiliated Hosp 1, Dept Endodont, Harbin, Peoples R China
推荐引用方式
GB/T 7714
Pan, Shuang,Dong, Qing,Sun, Li-Sha,et al. Mechanisms of Inactivation of PTCH1 Gene in Nevoid Basal Cell Carcinoma Syndrome: Modification of the Two-Hit Hypothesis[J]. CLINICAL CANCER RESEARCH,2010,16(2):442-450.
APA Pan, Shuang,Dong, Qing,Sun, Li-Sha,&Li, Tie-Jun.(2010).Mechanisms of Inactivation of PTCH1 Gene in Nevoid Basal Cell Carcinoma Syndrome: Modification of the Two-Hit Hypothesis.CLINICAL CANCER RESEARCH,16(2),442-450.
MLA Pan, Shuang,et al."Mechanisms of Inactivation of PTCH1 Gene in Nevoid Basal Cell Carcinoma Syndrome: Modification of the Two-Hit Hypothesis".CLINICAL CANCER RESEARCH 16.2(2010):442-450.
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