Molecular response to neoadjuvant chemotherapy in high-grade serous ovarian carcinoma

Rebecca C. Arend, Angelina I. Londoño, Allison M. Montgomery, Haller J. Smith, Zachary C. Dobbin, Ashwini A. Katre, Alba Martinez, Eddy S. Yang, Ronald D. Alvarez, Warner K. Huh, Kerri S. Bevis, J. Michael Straughn, Jacob M. Estes, Lea Novak, David K. Crossman, Sara J. Cooper, Charles N. Landen, Charles A. Leath

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41 Scopus citations

Abstract

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 ¼ 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. Implications: Gene expression profiles at the time of interval debulking provide additional genetic information that could help impact treatment decisions after NACT; although, continued collection and analysis of matched tumor and cfDNA from multiple time points are needed to determine the role of cfDNA in the management of HGSOC.

Original languageEnglish
Pages (from-to)813-824
Number of pages12
JournalMolecular Cancer Research
Volume16
Issue number5
DOIs
StatePublished - May 1 2018

Bibliographical note

Funding Information:
Circulogene Theranostics provided University of Alabama at Birmingham with cfDNA testing, and had no role in the control of the data and information submitted for publication. C.A. Leath III was supported by WRHR K-12 (5K12HD0012580-13), U–10 LAPS Grant (CA180855), and P30 Cancer Clinical Investigator Team Leadership Award (CCITLA; 3P30CA013148-43S3). R.C. Arend was supported by the ABOG/AAOG Early Career Development Grant, ACS_IRG Junior Faculty Development Grant (IRG-60-001-53 and P30 CA 013148), Norma Livingston Foundation Grant, Foundation for Women's Cancer Grant, and UAB CCTS Grant. A.I. Londoño was supported by T32 (5T32CA183926-02). S.J. Cooper was supported by the HudsonAlpha Tie the Ribbons Fund and the UAB CCTS Grant (NIH1UL1TR001417-01).

Publisher Copyright:
© 2018 American Association for Cancer Research.

ASJC Scopus subject areas

  • Medicine (all)

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