TONIC-Trial-cfDNA-Project

Cell-free DNA (cfDNA) is an emerging technology to predict and monitor response to cancer treatment, including immune checkpoint blockade (ICB). However, data on cfDNA dynamics during ICB in metastatic triple negative breast cancer (mTNBC) are limited. While most applications of cfDNA involve assays that focus on mutation detection, mTNBC and multiple other cancer types are driven by copy number alterations (CNAs). We evaluate cfDNA-based copy number profile abnormality (CPA) score as a potential biomarker for monitoring ICB response in mTNBC, analyzing data from 87 patients enrolled in stage 1 and stage 2 of the TONIC-trial. We find significant concordance between cfDNA-based and tissue-based CNA profiles. Additionally, responders show a decrease in CPA scores upon ICB at week 6 (3 cycles of nivolumab). These findings underscore the potential of cfDNA-based CNA dynamics as a non-invasive biomarker for ICB early response assessment in patients with mTNBC.

Type: Whole Genome Sequencing
Archiver: European Genome-Phenome Archive (EGA)

6 Datasets

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD50000001859	cfDNA shallow Whole-Genome sequencing on 15 samples derived from 5 paitnets with mTNBC, 3 technical replicates each, resulting 15 samples.	Illumina NovaSeq 6000	15
EGAD50000001860	sWGS of the blood samples from 14 (fourteen) healthy donors	Illumina HiSeq 2500	14
EGAD50000001861	cfDNA shallow Whole-Genome sequencing from 30 patients with mTNBC in the TONIC trial, including 2 timepoints: baseline and week 12.	Illumina HiSeq 2500	60
EGAD50000001862	cfDNA shallow Whole-Genome sequencing of the remaing patients with mTNBC in the TONIC trial, including 3 timepoints: baseline, week 6 and week 12. The week 6 data of the patients in the pilot run was sequenced here.	Illumina NovaSeq 6000	168
EGAD50000001863	14 TNBC tumors with tumor percentage ~90% were selected for in silico spike-in experiment	Illumina HiSeq 2500	14
EGAD50000001864	20 tumor tissue WES data with paired cfDNA sWGS data. This data is used for concordance analysis between cfDNA-based and tissue-based CNA. The WES libraries were sequenced across 3 independent runs using multiple lanes.	Illumina HiSeq 2500	80