Researchers at the OHSU Knight Cancer Institute recently found that sequencing the fragments of tumor DNA that circulate in blood may give a more accurate picture of a patient’s metastatic cancer than can be obtained from biopsies. Paul Spellman, Ph.D., professor of molecular and medical genetics at OHSU, led the study, which showed that whole-exome sequencing of cell-free DNA can find the same clinically relevant mutations identified in DNA from tumor tissue, and it can provide additional information about the evolution of a particular patient’s disease and how best to treat it. That’s significant because drawing blood to obtain cell-free DNA is less invasive and safer for patients than taking a biopsy of tumor tissue. The “liquid biopsy” approach makes it feasible to repeatedly sample tumor DNA over the course of treatment.
Taking biopsies at multiple metastatic sites often isn’t possible, for instance, when they are located in tissues that are difficult to access. Some lesions are too small to obtain enough tissue. And because tumors often consist of genetically heterogeneous cells, a biopsy needle can miss important mutations that arose outside the sampled area. Cell-free DNA in the blood stream, released from normal and cancerous cells when they die, offers an attractive way around these problems.
Researchers elsewhere have shown that whole-exome sequencing of cell-free DNA provides information comparable to that obtained from biopsies. But in previous work, tumor DNA made up an unusually large proportion of the cell-free DNA — from 33 to 65 percent — leaving it unclear how practical the approach could be. The OHSU researchers showed that it’s feasible in more typical cases when tumor DNA makes up only a small fraction of the cell-free DNA, less than 8 percent.
The study – “Exome sequencing of cell-free DNA from metastatic cancer patients identifies clinically actionable mutations distinct from primary disease” – was published last month in the open access journal PLOS ONE.