Journal
MOLECULAR CANCER RESEARCH
Volume 16, Issue 5, Pages 813-824Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-17-0594
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Funding
- WRHR K-12 [5K12HD0012580-13]
- U-10 LAPS Grant [CA180855]
- P30 Cancer Clinical Investigator Team Leadership Award (CCITLA) [3P30CA013148-43S3]
- ABOG/AAOG Early Career Development Grant
- ACS_IRG Junior Faculty Development Grant [IRG-60-001-53, P30 CA 013148]
- Norma Livingston Foundation Grant
- Foundation for Women's Cancer Grant
- UAB CCTS Grant
- HudsonAlpha Tie the Ribbons Fund
- UAB CCTS Grant [NIH1UL1TR001417-01]
- [5T32CA183926-02]
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While high-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants [by DNA next-generation sequencing (NGS) using a 50 gene Ion Torrent panel] and gene expression (using the NanoString PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT). NGS was performed on plasma cell free DNA (cfDNA) on a select group of patients (n = 14) to assess the utility of using cfDNA to monitor these changes. A total of 86 genes had significant changes in RNA expression after NACT. Thirty-eight genetic variants (including SNPs) from 6 genes were identified in tumors pre-NACT, while 59 variants from 19 genes were detected in the cfDNA. The number of DNA variants were similar after NACT. Of the 59 variants in the plasma pre-NACT, only 6 persisted, whereas 33 of 38 specific variants in the tumor DNA remained unchanged. Pathway analysis showed the most significant alterations in the cell cycle and DNA damage pathways. (C) 2018 AACR.
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