Open Access

Changes in the gene mutation profiles of circulating tumor DNA detected using CAPP‑Seq in neoadjuvant chemotherapy‑treated advanced ovarian cancer

  • Authors:
    • Tomoko Noguchi
    • Kazuko Sakai
    • Naoyuki Iwahashi
    • Kaho Matsuda
    • Hitomi Matsukawa
    • Tamaki Yahata
    • Saori Toujima
    • Kazuto Nishio
    • Kazuhiko Ino
  • View Affiliations

  • Published online on: January 28, 2020     https://doi.org/10.3892/ol.2020.11356
  • Pages: 2713-2720
  • Copyright: © Noguchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cancer Personalized Profiling by deep Sequencing (CAPP‑Seq) is a novel ultrasensitive next‑generation sequencing‑based approach that is used to detect circulating tumor DNA (ctDNA). The aim of the present study was to compare the gene mutation profiles and blood tumor mutation burden (bTMB) measured between pre‑ and post‑neoadjuvant chemotherapy (NAC), utilizing CAPP‑seq for plasma ctDNA in patients with advanced ovarian cancer. The current study included 10 patients (6 NAC‑sensitive and 4 NAC‑resistant) clinically diagnosed as having stage III or IV ovarian cancer and were administered NAC between May 2017 and February 2019. The plasma ctDNA samples were collected at pre‑ and post‑NAC, and comprehensive gene mutation analysis was performed using CAPP‑seq. In 5 out of 6 NAC‑sensitive cases, the variant allele frequency (VAF) of non‑synonymous somatic mutations decreased following NAC. In 2 out of the 4 NAC‑resistant cases, the VAF of non‑synonymous somatic mutations increased, and new somatic mutations emerged following NAC. In regard to TP53 mutation, the rate of TP53 mutation in the NAC‑resistant cases was significantly higher compared with NAC‑sensitive cases. Finally, the bTMB decreased significantly after NAC treatment in the NAC‑sensitive cases, even though there were no significant differences in the pretreatment bTMB levels between the NAC‑sensitive and NAC‑resistant cases. These results indicated that gene mutation can be profiled and monitored using liquid biopsy‑based CAPP‑Seq in patients with advanced ovarian cancer with NAC treatment, and TP53 mutation in the ctDNA and bTMB may be novel biomarkers that can be used for patient monitoring during NAC treatment.
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April-2020
Volume 19 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Noguchi T, Sakai K, Iwahashi N, Matsuda K, Matsukawa H, Yahata T, Toujima S, Nishio K and Ino K: Changes in the gene mutation profiles of circulating tumor DNA detected using CAPP‑Seq in neoadjuvant chemotherapy‑treated advanced ovarian cancer. Oncol Lett 19: 2713-2720, 2020
APA
Noguchi, T., Sakai, K., Iwahashi, N., Matsuda, K., Matsukawa, H., Yahata, T. ... Ino, K. (2020). Changes in the gene mutation profiles of circulating tumor DNA detected using CAPP‑Seq in neoadjuvant chemotherapy‑treated advanced ovarian cancer. Oncology Letters, 19, 2713-2720. https://doi.org/10.3892/ol.2020.11356
MLA
Noguchi, T., Sakai, K., Iwahashi, N., Matsuda, K., Matsukawa, H., Yahata, T., Toujima, S., Nishio, K., Ino, K."Changes in the gene mutation profiles of circulating tumor DNA detected using CAPP‑Seq in neoadjuvant chemotherapy‑treated advanced ovarian cancer". Oncology Letters 19.4 (2020): 2713-2720.
Chicago
Noguchi, T., Sakai, K., Iwahashi, N., Matsuda, K., Matsukawa, H., Yahata, T., Toujima, S., Nishio, K., Ino, K."Changes in the gene mutation profiles of circulating tumor DNA detected using CAPP‑Seq in neoadjuvant chemotherapy‑treated advanced ovarian cancer". Oncology Letters 19, no. 4 (2020): 2713-2720. https://doi.org/10.3892/ol.2020.11356