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. 2021 Apr 9:27:581534.
doi: 10.3389/pore.2021.581534. eCollection 2021.

Hybrid Capture-based Genomic Profiling of Circulating Tumor DNA From Patients With Advanced Ovarian Cancer

Wenbin Shen  1 , Boer Shan  1 , Shanhui Liang  1 , Junling Zhang  2 , Yangyang Yu  2 , Yuzi Zhang  2 , Guoqiang Wang  2 , Yuezong Bai  2 , Bing Qian  3 , Jin Lu  3 , Zhi Jiang  3
Affiliations

Hybrid Capture-based Genomic Profiling of Circulating Tumor DNA From Patients With Advanced Ovarian Cancer

Wenbin Shen et al. Pathol Oncol Res. .

Abstract

Objective: We conducted this study to characterize somatic genomic alterations in circulating tumor DNA (ctDNA) from patients with ovarian cancer and compare GAs detected in ctDNA with tissue databases. Methods: Hybrid capture-next generation sequencing genomic profiling of 150 genes was performed on ctDNA from 138 patients with ovarian cancer with 1,500× sequencing depth. The GAs detected in ctDNA were compared with those in our ovarian cancer tissue database (N = 488) and the Cancer Genome Atlas (TCGA) database (N = 489). Results: 115 patients (83%) had at least 1 GA detected in ctDNA. The most frequently altered genes detected in ctDNA were TP53 (72%), KRAS (11%), LRP1B (10%), ZNF703 (9%) and NF1 (8%). Comparative analysis with our tissue database showed similar frequencies of GAs per gene, although PIK3CA and KRAS mutations were more frequent in tissue and ctDNA, respectively (p < 0.05). Gene amplification and rearrangement were more frequent in ctDNA samples. The mutation frequency of homologous recombination repair associated-genes, VEGF signal/angiogenesis pathways, RAS pathways, NOTCH pathways and MSI-H ratio was not statistically different either in ctDNA or in tissue database. However, the mutation frequency of AKT, PIK3CA, PTEN and STK11 in PI3K/AKT/mTOR pathway was significantly lower than that in tissue samples (p < 0.05). Conclusions: Our results suggest that genomic profiling of ctDNA could detect somatic GAs in a significant subset of patients with ovarian cancer. Hybrid capture-NGS based on liquid biopsy has the potential capability to serve as a substitute to tissue biopsy and further studies are warranted.

Keywords: circulating tumor DNA; genomic alterations; genomic profiling; liquid biopsy; ovarian cancer.

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Conflict of interest statement

JZ, YY, YZ, GW, and YB were employed by the company 3D Medicines Inc., Shanghai, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The most frequent genomic alterations identified in circulating tumor DNA (ctDNA) from patients with ovarian cancer vs. in tissue. Samples with evidence of ctDNA in the blood (maximum somatic allele frequency >0) are included (A) Longtail of frequently altered genes in ovarian cancer. B-D. Comparison of the most frequently mutated (B), amplified (C), or rearranged (D) genes observed in ctDNA in this study with tissue-based genomic profiling of ovarian cancer cases or with a published tissue-based genomic profiling study of ovarian cancer (The Cancer Genome Atlas [TCGA], 2011). Data from the TCGA study were extracted from the cBioPortal.
FIGURE 2
FIGURE 2
Distribution of individual gene alterations within pathways identified in circulating tumor DNA (ctDNA) from patients with ovarian cancer vs. in tissue. (A) HRR associated-pathways. (B) PI3K/AKT/mTOR pathways. (C) VEGF signal/angiogenesis pathways. (D) RAS pathways. (E) NOTCH pathways. (F) The ratio of dMMR/MSI-H.
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