DNA methylation marker to estimate ovarian cancer cell fraction

Evaluation of a cancer cell fraction is important for accurate molecular analysis, and pathological analysis is the gold standard for evaluation. Despite the potential convenience, no established molecular markers for evaluation are available. In this study, we aimed to identify ovarian cancer cell...

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Published in:Medical oncology (Northwood, London, England) London, England), 2022-05, Vol.39 (5), p.78-78, Article 78
Main Authors: Ebata, Takahiro, Yamashita, Satoshi, Takeshima, Hideyuki, Yoshida, Hiroshi, Kawata, Yoshiko, Kino, Nao, Yasugi, Toshiharu, Terao, Yasuhisa, Yonemori, Kan, Kato, Tomoyasu, Ushijima, Toshikazu
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - genetics
Cell Line, Tumor
DNA Methylation
DNA, Neoplasm - genetics
Female
Genetic Markers
Hematology
Humans
Internal Medicine
Kruppel-Like Transcription Factors - genetics
Medicine
Medicine & Public Health
Oncology
Original Paper
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
Pathology
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Summary:Evaluation of a cancer cell fraction is important for accurate molecular analysis, and pathological analysis is the gold standard for evaluation. Despite the potential convenience, no established molecular markers for evaluation are available. In this study, we aimed to identify ovarian cancer cell fraction markers using DNA methylation highly specific to ovarian cancer cells. Using genome-wide DNA methylation data, we screened candidate marker genes methylated in 30 ovarian cancer FFPE samples and 12 high-grade serous ovarian cancer cell lines, and unmethylated in two female leucocytes and two normal fallopian epithelial cell samples. Methylation levels of two genes, SIM1 , and ZNF154 , showed high correlation with pathological cancer cell fractions among the 30 ovarian cancer FFPE samples ( R  = 0.61 for SIM1 , 0.71 for ZNF154 ). For cost-effective analysis of FFPE samples, pyrosequencing primers were designed, and successfully established for SIM1 and ZNF154 . Correlation between a pathological cancer cell fraction and methylation levels obtained by pyrosequencing was confirmed to be high ( R  = 0.53 for SIM1 , 0.64 for ZNF154 ). Finally, an independent validation cohort of 29 ovarian cancer FFPE samples was analyzed. ZNF154 methylation showed a high correlation with the pathological cancer cell fraction ( R  = 0.77, P  
ISSN:1357-0560
1559-131X
DOI:10.1007/s12032-022-01679-y