Profiling of circulating free DNA using targeted and genome-wide sequencing in patients with SCLC

Mohan, S. et al. (2020) Profiling of circulating free DNA using targeted and genome-wide sequencing in patients with SCLC. Journal of Thoracic Oncology, 15(2), pp. 216-230. (doi: 10.1016/j.jtho.2019.10.007) (PMID:31629061) (PMCID:PMC7001105)

[img]
Preview
Text
214528.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

2MB

Abstract

Introduction: SCLC accounts for approximately 250,000 deaths worldwide each year. Acquisition of adequate tumor biopsy samples is challenging, and liquid biopsies present an alternative option for patient stratification and response monitoring. Methods: We applied whole genome next-generation sequencing to circulating free DNA (cfDNA) from 39 patients with limited-stage (LS) SCLC and 30 patients with extensive-stage SCLC to establish genome-wide copy number aberrations and also performed targeted mutation analysis of 110 SCLC associated genes. Quantitative metrics were calculated for copy number aberrations, including percent genome amplified (PGA [the percentage of genomic regions amplified]), Z-score (a measure of standard deviation), and Moran’s I (a measure of spatial autocorrelation). In addition CellSearch, an epitope-dependent enrichment platform, was used to enumerate circulating tumor cells (CTCs) from a parallel blood sample. Results: Genome-wide and targeted cfDNA sequencing data identified tumor-related changes in 94% of patients with LS SCLC and 100% of patients with extensive-stage SCLC. Parallel analysis of CTCs based on at least 1 CTC/7.5 mL of blood increased tumor detection frequencies to 95% for LS SCLC. Both CTC counts and cfDNA readouts correlated with disease stage and overall survival. Conclusions: We demonstrate that a simple cfDNA genome-wide copy number approach provides an effective means of monitoring patients through treatment and show that targeted cfDNA sequencing identifies potential therapeutic targets in more than 50% of patients. We are now incorporating this approach into additional studies and trials of targeted therapies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Miller, Professor Crispin
Authors: Mohan, S., Foy, V., Ayub, M., Leong, H. S., Schofield, P., Sahoo, S., Descamps, T., Kilerci, B., Smith, N. K., Carter, M., Priest, L., Zhou, C., Carr, T. H., Miller, C., Faivre-Finn, C., Blackhall, F., Rothwell, D. G., Dive, C., and Brady, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Thoracic Oncology
Publisher:Elsevier
ISSN:1556-0864
ISSN (Online):1556-1380
Published Online:16 October 2019
Copyright Holders:Copyright ª 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
First Published:First published in Journal of Thoracic Oncology 15(2):216-230
Publisher Policy:Reproduced under a Creative Commons Licence

University Staff: Request a correction | Enlighten Editors: Update this record