Over three years, researchers at the University of Cambridge took surgical tumor samples (biopsies) and blood samples from a patient with ER-positive and HER2-positive breast cancer that had already spread to other parts of her body. They carefully studied small fragments of DNA from dying tumor cells that are shed into the blood, comparing them with DNA from the biopsy that was taken at the same point in time.
They characterized genomic architecture and infer clonal evolution in eight tumor biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing.
The results show that the DNA in the blood samples matched up with that from the biopsies, reflecting the same pattern and timing of genetic changes appearing as the cancer developed and responded to treatment.
Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumor biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites.
Researchers were even able to distinguish between the different secondary cancers and examine how each of the tumors was responding to treatment.
The results provide the first proof-of-principle that analysing tumour DNA in the blood can accurately monitor cancer within the body.