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

Study ID Alternative Stable ID Type
EGAS00001000625 Other

Study Description

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.

Study Datasets 3 datasets.

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Dataset ID Description Technology Samples
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
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
We used targeted deep sequencing to accurately establish the allele frequencies of the mutations identified by exome sequencing
Illumina MiSeq 23

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