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01.05.2022 | Original Paper

DNA methylation marker to estimate ovarian cancer cell fraction

verfasst von: Takahiro Ebata, Satoshi Yamashita, Hideyuki Takeshima, Hiroshi Yoshida, Yoshiko Kawata, Nao Kino, Toshiharu Yasugi, Yasuhisa Terao, Kan Yonemori, Tomoyasu Kato, Toshikazu Ushijima

Erschienen in: Medical Oncology | Ausgabe 5/2022

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Abstract

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 < 0.0001). Therefore, the ZNF154 methylation level was considered to be useful for the estimation of ovarian cancer cell fraction, and is expected to help accurate molecular analysis.

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Titel: DNA methylation marker to estimate ovarian cancer cell fraction
verfasst von: Takahiro Ebata
Satoshi Yamashita
Hideyuki Takeshima
Hiroshi Yoshida
Yoshiko Kawata
Nao Kino
Toshiharu Yasugi
Yasuhisa Terao
Kan Yonemori
Tomoyasu Kato
Toshikazu Ushijima
Publikationsdatum: 01.05.2022
Verlag: Springer US
Erschienen in: Medical Oncology / Ausgabe 5/2022
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-022-01679-y

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Springer Medizin

DNA methylation marker to estimate ovarian cancer cell fraction

Abstract

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Abstract

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