Unique genomic alterations of cerebrospinal fluid cell-free DNA are critical for targeted therapy of non-small cell lung cancer with leptomeningeal metastasis

Yongsheng Wang; Feng Jiang; Yijie Zhang; Ming Li; Yan Li; Hui Li; Qi Zhao; Mingke Shi; Yanzhe Yu; Yang W Shao; Hourong Cai; Liyun Miao; Hongping Xia

doi:10.1016/j.ygeno.2021.11.015

Unique genomic alterations of cerebrospinal fluid cell-free DNA are critical for targeted therapy of non-small cell lung cancer with leptomeningeal metastasis

Genomics. 2021 Nov 15:S0888-7543(21)00398-0. doi: 10.1016/j.ygeno.2021.11.015. Online ahead of print.

Authors

Yongsheng Wang¹, Feng Jiang², Yijie Zhang³, Ming Li¹, Yan Li¹, Hui Li¹, Qi Zhao¹, Mingke Shi¹, Yanzhe Yu¹, Yang W Shao⁴, Hourong Cai⁵, Liyun Miao⁶, Hongping Xia⁷

Affiliations

¹ Department of Respiratory Medicine & Radiology & Cardiothoracic Surgery, Nanjing Drum Tower Hospital Affiliated to Medical school of Nanjing University, Nanjing 210008, China.
² The First Affiliated Hospital/Yijishan Hospital of Wannan Medical School, Wuhu 241000, China.
³ Department of Respiratory and Critical Care Medicine, Henan University Huaihe Hospital, Kaifeng 475000, China.
⁴ Nanjing Geneseeq Technology Inc., Nanjing 210032, China.
⁵ Department of Respiratory Medicine & Radiology & Cardiothoracic Surgery, Nanjing Drum Tower Hospital Affiliated to Medical school of Nanjing University, Nanjing 210008, China. Electronic address: caihourong@yeah.net.
⁶ Department of Respiratory Medicine & Radiology & Cardiothoracic Surgery, Nanjing Drum Tower Hospital Affiliated to Medical school of Nanjing University, Nanjing 210008, China. Electronic address: liyunmiao462@163.com.
⁷ Department of Pathology, School of Basic Medical Sciences & Sir Run Run Hospital& State Key Laboratory of Reproductive Medicine & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing 211166, China. Electronic address: xiahongping@njmu.edu.cn.

PMID: 34793951
DOI: 10.1016/j.ygeno.2021.11.015

Abstract

We reported unique molecular features of cerebrospinal fluid (CSF) of NSCLC patients with leptomeningeal metastasis (LM), suggesting to establish CSF as a better liquid biopsy in clinical practices. We performed next-generation panel sequencing of primary tumor tissue, plasma and CSF from 131 NSCLC patients with LM, and observed high somatic copy number variations (CNV) in CSF of NSCLC patients with LM. The status of EGFR-activating mutations was highly concordant between CSF, plasma, and primary tumors. ALK translocation was detected in 8.3% of tumor tissues, but only 2.4% in CSF and 2.7% in plasma. Others such as ROS1 rearrangement, RET fusion, HER2 mutation, NTRK1 fusion, and BRAF V600E mutation were detected in 7.9% of CSF and 11.1% of tumor tissues, but only 4% in plasma. Our study has shed light on the unique genomic variations of CSF and demonstrated that CSF may represent better liquid biopsy for NSCLC patients with LM.

Keywords: Cell free DNA; Cerebrospinal fluid; Leptomeningeal metastasis; Liquid biopsy; Non-small cell lung cancer.