TY  - JOUR
AU  - Janke, Florian
AU  - Gasser, Mateo
AU  - Angeles, Arlou K
AU  - Riediger, Anja L
AU  - Görtz, Magdalena
AU  - Appenheimer, Louise
AU  - Laut, Astrid K
AU  - Ogrodnik, Simon
AU  - Gerhardt, Sabrina
AU  - Stenzinger, Albrecht
AU  - Schneider, Marc A
AU  - Thomas, Michael
AU  - Christopoulos, Petros
AU  - Sültmann, Holger
TI  - Low-coverage whole genome sequencing of cell-free DNA to predict and track immunotherapy response in advanced non-small cell lung cancer.
JO  - Journal of experimental & clinical cancer research
VL  - 44
IS  - 1
SN  - 0392-9078
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2025-00523
SP  - 87
PY  - 2025
N1  - #EA:B063#LA:B063#
AB  - Outcomes under anti-PD-(L)1 therapy have been variable in advanced non-small cell lung cancer (NSCLC) without reliable predictive biomarkers so far. Targeted next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) has demonstrated potential clinical utility to support clinical decisions, but requires prior tumor genetic profiling for proper interpretation, and wide adoption remains limited due to high costs.Tumor-agnostic low-coverage ctDNA whole genome sequencing (lcWGS) was used to longitudinally track genome-wide copy number variations (CNVs) and fragmentation features in advanced NSCLC patients (n = 118 samples from 49 patients) and healthy controls (n = 57). Tumor PD-L1 expression was available for comparison.Fragmentation features and CNVs were complementary indicators, whose combination significantly increased ctDNA detection compared to single-marker assessments (+ 20.3
KW  - Humans
KW  - Carcinoma, Non-Small-Cell Lung: genetics
KW  - Carcinoma, Non-Small-Cell Lung: drug therapy
KW  - Carcinoma, Non-Small-Cell Lung: pathology
KW  - Carcinoma, Non-Small-Cell Lung: immunology
KW  - Lung Neoplasms: genetics
KW  - Lung Neoplasms: drug therapy
KW  - Lung Neoplasms: pathology
KW  - Lung Neoplasms: immunology
KW  - Male
KW  - Female
KW  - Middle Aged
KW  - Aged
KW  - Whole Genome Sequencing: methods
KW  - Immunotherapy: methods
KW  - Cell-Free Nucleic Acids: genetics
KW  - Circulating Tumor DNA: genetics
KW  - Circulating Tumor DNA: blood
KW  - DNA Copy Number Variations
KW  - Biomarkers, Tumor: genetics
KW  - Adult
KW  - Aged, 80 and over
KW  - CfDNA fragmentation (Other)
KW  - Copy number variations (Other)
KW  - Immunotherapy (Other)
KW  - Liquid biopsy (Other)
KW  - Low-coverage whole genome sequencing (Other)
KW  - Non-small cell lung cancer (Other)
KW  - Response prediction (Other)
KW  - Cell-Free Nucleic Acids (NLM Chemicals)
KW  - Circulating Tumor DNA (NLM Chemicals)
KW  - Biomarkers, Tumor (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40055810
C2  - pmc:PMC11889826
DO  - DOI:10.1186/s13046-025-03348-0
UR  - https://inrepo02.dkfz.de/record/299582
ER  -