Divergence between high metastatic tumor burden and low circulating tumor DNA concentration in metastasized breast cancer

Circulating tumor DNA (ctDNA) was reported to represent a highly sensitive biomarker of metastatic cancer disease directly reflecting tumor burden and dynamics. Here we investigated the role of ctDNA in patients with metastatic breast cancer. In an index patient with more than 100,000 circulating tumor cells (CTCs) in serial blood analyses, whole genome, exome, or targeted deep sequencing of the primary tumor, metastases, and 551 CTCs were consistent with a genetically homogeneous cancer. However, the allele fractions (AFs) of ctDNA were only 2-3% in each analysis, which did neither reflect the tumor burden nor the dynamics of this progressive disease by far. Indeed, plasma analyses of 71 further patients demonstrated highly variable AFs of mutant fragments, which frequently did not correspond to the tumor burden. These results provide insights into mechanisms involved in CTC and ctDNA release into the circulation and have important implications for diagnostic tests based on liquid biopsies.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

3 Datasets 1 Publication

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
EGAD00001000761	In order to establish copy number profiles from the various samples we prepared libraries and subjected them to whole-genome sequencing at a shallow sequencing depth (0.1x)	Illumina MiSeq	14
EGAD00001000762	We utilized exome sequencing for DNA obtained from saliva (germline DNA) and the four spatially separated tumor foci and 3 corresponding lymph node metastases	Illumina HiSeq 2000	8
EGAD00001000763	We used targeted deep sequencing to accurately establish the allele frequencies of the mutations identified by exome sequencing	Illumina MiSeq	23

Publications	Citations
The dynamic range of circulating tumor DNA in metastatic breast cancer. Heidary M, Auer M, Ulz P, Heitzer E, Petru E, Gasch C, Riethdorf S, Mauermann O, Lafer I, Pristauz G, Lax S, Pantel K, Geigl JB, Speicher MR. Breast Cancer Res 16: 2014 421	67