%0 Journal Article
%A Janke, Florian
%A Gasser, Mateo
%A Angeles, Arlou K
%A Riediger, Anja L
%A Görtz, Magdalena
%A Appenheimer, Louise
%A Laut, Astrid K
%A Ogrodnik, Simon
%A Gerhardt, Sabrina
%A Stenzinger, Albrecht
%A Schneider, Marc A
%A Thomas, Michael
%A Christopoulos, Petros
%A Sültmann, Holger
%T Low-coverage whole genome sequencing of cell-free DNA to predict and track immunotherapy response in advanced non-small cell lung cancer.
%J Journal of experimental & clinical cancer research
%V 44
%N 1
%@ 0392-9078
%C Heidelberg
%I Springer
%M DKFZ-2025-00523
%P 87
%D 2025
%Z #EA:B063#LA:B063#
%X 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
%K Humans
%K Carcinoma, Non-Small-Cell Lung: genetics
%K Carcinoma, Non-Small-Cell Lung: drug therapy
%K Carcinoma, Non-Small-Cell Lung: pathology
%K Carcinoma, Non-Small-Cell Lung: immunology
%K Lung Neoplasms: genetics
%K Lung Neoplasms: drug therapy
%K Lung Neoplasms: pathology
%K Lung Neoplasms: immunology
%K Male
%K Female
%K Middle Aged
%K Aged
%K Whole Genome Sequencing: methods
%K Immunotherapy: methods
%K Cell-Free Nucleic Acids: genetics
%K Circulating Tumor DNA: genetics
%K Circulating Tumor DNA: blood
%K DNA Copy Number Variations
%K Biomarkers, Tumor: genetics
%K Adult
%K Aged, 80 and over
%K CfDNA fragmentation (Other)
%K Copy number variations (Other)
%K Immunotherapy (Other)
%K Liquid biopsy (Other)
%K Low-coverage whole genome sequencing (Other)
%K Non-small cell lung cancer (Other)
%K Response prediction (Other)
%K Cell-Free Nucleic Acids (NLM Chemicals)
%K Circulating Tumor DNA (NLM Chemicals)
%K Biomarkers, Tumor (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40055810
%2 pmc:PMC11889826
%R 10.1186/s13046-025-03348-0
%U https://inrepo02.dkfz.de/record/299582