- Gynecologic cancer
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Evaluation of Circulating Tumor DNA in Patients with Ovarian Cancer Harboring Somatic PIK3CA or KRAS Mutations
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Aiko Ogasawara, Taro Hihara, Daisuke Shintani, Akira Yabuno, Yuji Ikeda, Kenji Tai, Keiichi Fujiwara, Keisuke Watanabe, Kosei Hasegawa
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Cancer Res Treat. 2020;52(4):1219-1228. Published online May 6, 2020
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DOI: https://doi.org/10.4143/crt.2019.688
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 Abstract
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- Purpose
Circulating tumor DNA (ctDNA) is an attractive source for liquid biopsy to understand molecular phenotypes of a tumor non-invasively, which is also expected to be both a diagnostic and prognostic marker. PIK3CA and KRAS are among the most frequently mutated genes in epithelial ovarian cancer (EOC). In addition, their hotspot mutations have already been identified and are ready for a highly sensitive analysis. Our aim is to clarify the significance of PIK3CA and KRAS mutations in the plasma of EOC patients as tumor-informed ctDNA.
Methods
We screened 306 patients with ovarian tumors for somatic PIK3CA or KRAS mutations. A total of 85 EOC patients had somatic PIK3CA and/or KRAS mutations, and the corresponding mutations were subsequently analyzed using a droplet digital polymerase chain reaction in their plasma.
Results
The detection rates for ctDNA were 27% in EOC patients. Advanced stage and positive peritoneal cytology were associated with higher frequency of ctDNA detection. Preoperative ctDNA detection was found to be an indicator of outcomes, and multivariate analysis revealed that ctDNA remained an independent risk factor for recurrence (p=0.010). Moreover, we assessed the mutation frequency in matched plasma before surgery and at recurrence from 17 patients, and found six patients had higher mutation rates in cell-free DNA at recurrence compared to that at primary diagnosis.
Conclusion
The presence of ctDNA at diagnosis was an indicator for recurrence, which suggests potential tumor spread even when tumors were localized at the time of diagnosis.
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Citations
Citations to this article as recorded by  - Liquid biopsy in gynecological cancers: a translational framework from molecular insights to precision oncology and clinical practice
Canio Martinelli, Alfredo Ercoli, Giuseppe Vizzielli, Sharon Raffaella Burk, Maria Cuomo, Vrunda Satasiya, Housem Kacem, Simone Braccia, Giulio Mazzarotti, Irene Miriello, Manuela Nana Tchamou, Stefano Restaino, Martina Arcieri, Alice Poli, Veronica Tius,
Journal of Experimental & Clinical Cancer Research.2025;[Epub] CrossRef - Circulating tumor DNA as a biomarker for predicting progression-free survival and overall survival in patients with epithelial ovarian cancer: a systematic review and meta-analysis
Cristina Taliento, Giampaolo Morciano, Camilla Nero, Wouter Froyman, Giuseppe Vizzielli, Matteo Pavone, Stefano Salvioli, Mara Tormen, Francesco Fiorica, Gennaro Scutiero, Giovanni Scambia, Carlotta Giorgi, Pantaleo Greco, Paolo Pinton
International Journal of Gynecologic Cancer.2024; : ijgc-2024-005313. CrossRef - DNA methylation marker to estimate ovarian cancer cell fraction
Takahiro Ebata, Satoshi Yamashita, Hideyuki Takeshima, Hiroshi Yoshida, Yoshiko Kawata, Nao Kino, Toshiharu Yasugi, Yasuhisa Terao, Kan Yonemori, Tomoyasu Kato, Toshikazu Ushijima
Medical Oncology.2022;[Epub] CrossRef - Detection of ESR1 Mutations in Primary Tumors and Plasma Cell-Free DNA in High-Grade Serous Ovarian Carcinoma Patients
Dimitra Stergiopoulou, Athina Markou, Lydia Giannopoulou, Paul Buderath, Ioanna Balgkouranidou, Nikolaos Xenidis, Stylianos Kakolyris, Sabine Kasimir-Bauer, Evi Lianidou
Cancers.2022; 14(15): 3790. CrossRef - Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer
Christen A. Khella, Gaurav A. Mehta, Rushabh N. Mehta, Michael L. Gatza
Journal of Personalized Medicine.2021; 11(2): 149. CrossRef - Tumor-related mutations in cell-free DNA in pre-operative plasma as a prognostic indicator of recurrence in endometrial cancer
Daisuke Shintani, Taro Hihara, Aiko Ogasawara, Sho Sato, Akira Yabuno, Kenji Tai, Keiichi Fujiwara, Keisuke Watanabe, Kosei Hasegawa
International Journal of Gynecological Cancer.2020; 30(9): 1340. CrossRef
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