Genomic profiling of the residual disease of advanced high-grade serous ovarian cancer after neoadjuvant chemotherapy |
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Authors: | Yong J Lee Dachan Kim Jung E Shim Su-Jin Bae Yu-Jin Jung Sora Kim Hanna Lee So H Kim Su B Jo Jung-Yun Lee Hyun-Soo Kim Soonmyung Paik |
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Affiliation: | 1. Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea;2. Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea;3. Department of Biomedical Systems Informatics, Bran Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea;4. Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea;5. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea |
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Abstract: | The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre-NAC and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K–AKT–mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K–AKT–mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC. |
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Keywords: | ovarian cancer high-grade serous carcinoma genomic profiling residual disease |
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