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学科主题: 口腔医学
题名:
Mechanisms of Inactivation of PTCH1 Gene in Nevoid Basal Cell Carcinoma Syndrome: Modification of the Two-Hit Hypothesis
作者: Pan, Shuang1,2,3; Dong, Qing1,2; Sun, Li-Sha1,2; Li, Tie-Jun1,2
刊名: CLINICAL CANCER RESEARCH
发表日期: 2010-01-15
DOI: 10.1158/1078-0432.CCR-09-2574
卷: 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
所属项目编号: 30625044 ; 30872900
项目资助者: National Nature Science Foundation of China
WOS记录号: WOS:000278545000010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55233
Appears in Collections:北京大学口腔医学院_口腔病理科_期刊论文

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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

Recommended Citation:
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.
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