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Genomic profiling of the residual disease of advanced high-grade serous ovarian cancer after neoadjuvant chemotherapy

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 
Citation
 INTERNATIONAL JOURNAL OF CANCER, Vol.146(7) : 1851-1861, 2020 
Journal Title
 INTERNATIONAL JOURNAL OF CANCER 
ISSN
 0020-7136 
Issue Date
2020
MeSH
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/pharmacology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Cell Cycle/genetics ; Cystadenocarcinoma, Serous/genetics* ; Cystadenocarcinoma, Serous/mortality ; Cystadenocarcinoma, Serous/therapy ; Cytoreduction Surgical Procedures/methods ; Disease Progression ; Drug Resistance, Neoplasm/genetics ; Female ; Genomics ; Humans ; Middle Aged ; Mutation/drug effects ; Neoadjuvant Therapy/methods ; Neoplasm, Residual ; Ovarian Neoplasms/genetics* ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/therapy ; Ovariectomy/methods ; Ovary/drug effects ; Ovary/pathology* ; Phosphatidylinositol 3-Kinases/metabolism ; Progression-Free Survival ; Proto-Oncogene Proteins c-akt/metabolism ; Retrospective Studies ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Survival Analysis ; TOR Serine-Threonine Kinases/metabolism
Keywords
genomic profiling ; high-grade serous carcinoma ; ovarian cancer ; residual disease
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.
Full Text
https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.32729
DOI
10.1002/ijc.32729
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyun-Soo(김현수)
Bae, Sujin(배수진)
Paik, Soon Myung(백순명) ORCID logo https://orcid.org/0000-0001-9688-6480
Lee, Yong Jae(이용재) ORCID logo https://orcid.org/0000-0003-0297-3116
Lee, Jung-Yun(이정윤) ORCID logo https://orcid.org/0000-0001-7948-1350
Lee, Hanna(이한나)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175482
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