Aberrant methylation of PCDH17 gene in high-grade serous ovarian carcinoma

被引:12
|
作者
Baranova, Ivana [1 ,2 ]
Kovarikova, Helena [1 ,2 ]
Laco, Jan [2 ,3 ]
Dvorak, Ondrej [2 ,4 ]
Sedlakova, Iva [2 ,4 ]
Palicka, Vladimir [1 ,2 ]
Chmelarova, Marcela [1 ,2 ]
机构
[1] Charles Univ Prague, Fac Med, Inst Clin Biochem & Diagnost, Hradec Kralove, Czech Republic
[2] Univ Hosp Hradec Kralove, Hradec Kralove, Czech Republic
[3] Charles Univ Prague, Fac Med, Fingerland Dept Pathol, Hradec Kralove, Czech Republic
[4] Charles Univ Prague, Fac Med, Dept Obstet & Gynecol, Hradec Kralove, Czech Republic
关键词
Ovary; high-grade serous carcinoma; methylation; protocadherin; next-generation sequencing; biomarker; PROMOTER METHYLATION; DNA METHYLATION; TUMOR-SUPPRESSOR; FALLOPIAN-TUBE; SIGNALING PATHWAY; PROTOCADHERIN; 10; BLADDER-CANCER; BREAST-CANCER; CELL-ADHESION; METASTASIS;
D O I
10.3233/CBM-181493
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: Aberrant DNA methylation of protocadherins (PCDHs) has been associated with development and progression of various types of cancer. It could represent possible direction in the search for critically needed tumor biomarkers for ovarian cancer. OBJECTIVE: To investigate methylation of delta 2 group of non-clustered PCDHs in high-grade serous ovarian carcinoma (HGSOC) tissue in comparison with control tissue. METHODS: We used next-generation sequencing for detecting regions with the most altered methylation. For further confirmation of discovered alterations we used methylation-sensitive high-resolution melting analysis. RESULTS: PCDH17 methylation was detected in almost 70% of HGSOC patients without any methylation in the group of control samples and was found both in the late stage tumors as well as in the early stage ones. Other selected PCDHs did not show any relevant changes in methylation. Subsequent gene expression analysis of PCDH17 revealed decreased expression in all of the tumor samples in comparison to the control ones. Statistically significant negative correlation was found between methylation and levels of expression suggesting potentially methylation-based silencing. CONCLUSIONS: Methylation of PCDH17 could play an important role in development and progression of HGSOC and has potential to become a target in the search for new clinical biomarkers.
引用
收藏
页码:125 / 133
页数:9
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