Profiling of Circulating Free DNA Using Targeted and Genome-wide Sequencing in Patients with SCLC.
J Thorac Oncol
; 15(2): 216-230, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31629061
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma Pulmonar de Células Pequeñas
/
Ácidos Nucleicos Libres de Células
/
Neoplasias Pulmonares
/
Células Neoplásicas Circulantes
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Thorac Oncol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Reino Unido