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Aberrant methylation of the PTCH1 gene promoter region in aberrant crypt foci
Author(s) -
Peng Liang,
Hu Jingjing,
Li Shujun,
Wang Zhongqiu,
Xia Bingqing,
Jiang Bo,
Li Bingsheng,
Zhang Yu,
Wang Jing,
Wang Xinying
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27812
Subject(s) - ptch1 , methylation , gli1 , biology , carcinogenesis , patched , dna methylation , aberrant crypt foci , microdissection , microbiology and biotechnology , immunohistochemistry , bisulfite sequencing , cancer research , colorectal cancer , cancer , hedgehog , gene expression , immunology , genetics , gene , colonic disease
Patched homolog 1 (PTCH1) is a known tumor suppressor that regulates the Hedgehog (Hh) pathway and has been implicated in tumorigenesis. The role of PTCH1 in colon carcinogenesis, however, is controversial. The aim of the present study was to investigate epigenetic modifications of PTCH1 in aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancer (CRC). Using laser‐capture microdissection (LCM), a pure population of ACF epithelial cells was isolated and studied. The inherent protein expression levels of SHH, PTCH1, SMO and GLI1 were assessed by immunohistochemistry for 405 ACF, including 54 dysplastic ACF (d‐ACF) and 351 non‐dysplastic ACF (n‐ACF). The mRNA levels and methylation status of PTCH1 were also determined in 54 d‐ACF and 96 n‐ACF. Our data showed that the expression of SHH, SMO and GLI1 was significantly up‐regulated in d‐ACF, compared to n‐ACF. Also, the mRNA and protein levels of PTCH1 were lower in d‐ACF than n‐ACF. Using MSP or MS‐HRM, PTCH1 methylation was present in 64.8% (35/54) or 63.3% (34/54), respectively, of d‐ACF and 19.8% (19/96) or 22.9% (11/48), respectively, of n‐ACF. PTCH1 methylation was more frequent in d‐ACF than n‐ACF ( p < 0.001) and was associated with PTCH1 mRNA levels ( r = 0.358, p < 0.01). There was a statistically significant correlation between PTCH1 methylation status and the prevalence of colorectal neoplasms. In conclusion, this study suggests that aberrant methylation of the PTCH1 promoter may be an early, initiating event of colon carcinogenesis.