Circulating Cell-Free DNA-Based Detection of Tumor Suppressor Gene Copy Number Loss and Its Clinical Implication in Metastatic Prostate Cancer

Xiaoxi Dong; Tiantian Zheng; Minhua Zhang; Chao Dai; Lili Wang; Lei Wang; Ruipeng Zhang; Yuan Long; Danyi Wen; Feng Xie; Yue Zhang; Yong Huang; Jianguo Dong; Huan Liu; Pan Du; Bonnie L King; Winston Tan; Shidong Jia; Chris X Lu; Manish Kohli; Haitao Wang; Jianjun Yu

doi:10.3389/fonc.2021.720727

Circulating Cell-Free DNA-Based Detection of Tumor Suppressor Gene Copy Number Loss and Its Clinical Implication in Metastatic Prostate Cancer

Front Oncol. 2021 Aug 24:11:720727. doi: 10.3389/fonc.2021.720727. eCollection 2021.

Authors

Xiaoxi Dong¹, Tiantian Zheng¹, Minhua Zhang², Chao Dai¹, Lili Wang³, Lei Wang³, Ruipeng Zhang², Yuan Long⁴, Danyi Wen⁵, Feng Xie⁶, Yue Zhang⁶, Yong Huang⁶, Jianguo Dong⁶, Huan Liu⁷, Pan Du¹, Bonnie L King¹, Winston Tan⁸, Shidong Jia¹, Chris X Lu⁹, Manish Kohli¹⁰, Haitao Wang³, Jianjun Yu¹

Affiliations

¹ Predicine Inc., Hayward, CA, United States.
² Department of Translational Medicine, Laekna Therapeutics Shanghai Co., Ltd., Shanghai, China.
³ Department of Oncology, Second Hospital of Tianjin Medical University, Tianjin, China.
⁴ Department of New Assay Development, Shanghai Lide Biotech Co., Ltd., Shanghai, China.
⁵ Shanghai Lide Biotech Co., Ltd., Shanghai, China.
⁶ Huidu Shanghai Medical Sciences Ltd., Shanghai, China.
⁷ Department of Biology, Shanghai Lide Biotech Co., Ltd., Shanghai, China.
⁸ Division of Medical Oncology, Department of Medicine, Mayo Clinic, Jacksonville, FL, United States.
⁹ Laekna Therapeutics Shanghai Co., Ltd., Shanghai, China.
¹⁰ Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, United States.

Abstract

Current liquid biopsy assays lack sufficient sensitivity to detect copy number loss, which limits the interrogation of critical tumor suppressor gene deletions during cancer progression and treatment. Here we describe a liquid biopsy assay with improved sensitivity for detection of copy number loss in blood samples with low levels of circulating tumor DNA, and demonstrate its utility by profiling PTEN, RB1, and TP53 genetic loss in metastatic prostate cancer patients.

Keywords: NGS; circulating tumor DNA; copy number loss; liquid biopsy; prostate cancer.