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Poster Display session 2

4288 - Hybrid capture-based genomic profiling of circulating tumor DNA (ctDNA) from patients with ovarian cancer

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Ovarian Cancer

Presenters

Mi Yang

Citation

Annals of Oncology (2019) 30 (suppl_5): v403-v434. 10.1093/annonc/mdz250

Authors

M. Yang1, Z. Jiang2, Y. Zhang3, S. Cai4

Author affiliations

  • 1 Gynecologic Oncology, Cancer Center of NanJing GaoChun People’s Hospital; The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University, 210009 - Nanjing/CN
  • 2 Department Of Gynecologic Oncology, Jiangsu cancer institute, Medical university nanjing cencer center, Jiangsu red cross cencer center, 210009 - Nanjing/CN
  • 3 The Medical Department, 3D Medicines Inc., 201114 - Shanghai/CN
  • 4 The Medical Departement, 3D Medicines Inc., 201114 - Shanghai/CN

Resources

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Abstract 4288

Background

Genomic profiling of blood-derived circulating tumour DNA (ctDNA) which is considered as a minimally invasive biopsy, has several potential applications in the management of ovarian cancer, including selection of targeted therapy, drug resistance prediction and the evaluation of treatment response. Therefore, we conducted this study to characterize genomic alterations (GA) in ctDNA from patients with ovarian cancer and compare GA detected in ctDNA with those detected in tissue databases.

Methods

Hybrid capture-based next generation sequencing (NGS) genomic profiling of 150 genes was performed on ctNDA from 76 patients with ovarian cancer in a CAP-accredited laboratory. The GA detected in ctDNA were compared with the 3D Med tissue database tested by NGS (N = 260) and TCGA database tested by whole-exon sequencing (N = 587). The fraction of ctDNA was estimated using the maximum somatic allele frequency (MSAF). GAs including single nucleotide variation (SNV), insertions/deletions, copy number variations, gene rearrangement and fusions were assessed. Germline alterations were excluded.

Results

89.5% (68/76) of patients (median age 57) detected ≥1 GA in ctDNA. Frequently altered genes detected in ctDNA for SNV were TP53 (52.6%), AR (11.8%), KRAS (9.2%), NOTCH2 (6.6%) and PIK3CA (5.3%) compared to 3D Med tissue database (median age 55) including 260 samples with TP53 (74.2%), AR (6.9%), KRAS (24.6%) NOTCH2 (11.5%) and PIK3CA (3.8%). In TCGA database including 587 patients with early stage diseases, the frequencies of the commonly altered genes detected in ctDNA were largely different with TP53 (65.9%), AR (1.0%), KRAS (1.0%), NOTCH2 (1.2%) and PIK3CA (2.6%). Alterations in five DNA damage repair associated-genes including BRCA1, BRCA2, ATM, ATR, RAD50 and CHEK2 were detected in 14.5% (11/76) of patients in ctDNA database compared to 19.2% (50/260) of patients in 3D Med tissue database and 12.6% (74/587) of patients in TCGA database.

Conclusions

Our results suggest that genomic profiling of ctDNA could detected GAs in a significant subset of patients with ovarian cancer. Hybrid capture- NGS based ctDNA liquid biopsy has the potential capability to serve as an alternative to tissue biopsy and further studies are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

NanJing GaoChun People’s Hospital.

Funding

Has not received any funding.

Disclosure

Y. Zhang: Full / Part-time employment: 3D Medicines Inc. S. Cai: Full / Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.

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