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Methylation and expression analysis of mismatch repair genes in extramammary Paget's disease
Author(s) -
Kang Z.,
Zhu Y.,
Zhang Q.A.,
Dong L.,
Xu F.,
Zhang X.,
Guan M.
Publication year - 2019
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.15404
Subject(s) - cpg site , methylation , dna methylation , promoter , gene , immunohistochemistry , cancer research , bisulfite sequencing , medicine , microbiology and biotechnology , gene expression , biology , genetics , pathology
Background Extramammary Paget's disease ( EMPD ) is a rare skin cancer with relative high frequencies of germline and somatic mismatch repair ( MMR ) genes mutations. However, the methylation and expression of these genes have not been validated in EMPD . Objective This study aims to confirm the methylation and expression of MMR genes in EMPD . Methods Immunohistochemical ( IHC ) staining detection and Methylation‐specific PCR ( MSP ) were used to analyse MLH 1, MSH 2, MSH 6 and PMS 2 proteins’ expression and promoters’ methylation in 57 EMMD samples, and pyro‐sequence was used to find highly methylated CpG sites in MSH 2 promoter. Results Immunohistochemical detection displayed reduced expression of MSH 2 in 38.6% EMPD cases but normal expression of MLH 1, MSH 6 and PMS 2 in all tumour tissues. Hypermethylation also was found in the promoter of MSH 2 but not in other MMR genes. Pyrosequencing of MSH 2 promoter showed CpG6 (‐87) and CpG3 (‐98) were the most common two methylated CpG dinucleotides. There is a significant correlation between reduced MSH 2 expression and MSH 2 methylation. Conclusion Reduced MSH 2 expression and hypermethylation in this gene promoter were common genetic changes in EMPD , which expands our understanding of the role of MMR function in this skin cancer.