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. Mol Cancer Res; 16(5); 813-24. Ó2018 AACR.

Recent regulatory approval of novel treatment options has significantly expanded the therapeutic armamentarium, and the addition of these therapies has challenged clinicians to select and optimally sequence these compounds. This review will focus on examination of current guidelines and consensus building for optimal sequencing of systemic therapies for advanced or recurrent uterine leoimyosarcoma.

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<p>Supplementary Table and Figure Legends</p>

<p>R-plot PCA by cellularity.</p>

<p>Table 1. Tumor Histology, Cellularity, and Chemotherapy Respons. Table 2. Significance and Fold Change of 770 genes and corresponding pathways in pre- and post-NACT. Table 3. List of top canonical pathways, molecular and cellular function, toxicity list, and networks. Table 4. Classification of all variants identified in DNA and cell-free DNA of pre- and post-NACT. Protein Change. Table 5. Number of mutant genes and specific variants in pre- and post-NAC. Table 6. All variants in pre- and post-NACT and recurrent plasma samples.Table 7. Potential FDA-approved targeted therapies and clinical trials based on gene level alterations.</p>

<p>Plasma cfDNA vs. Tumor DNA variant overlap.</p>