By Magdalena Kegel
December 22, 2017
A blood test may one day replace tumor tissue sampling for patients with prostate cancer, as research shows that nearly 90 percent of a tumor’s genetic features can be detected in the blood.
Such blood biopsies may make it easier for physicians to choose treatment, and monitor a patient for disease progression and treatment response, said researchers behind a recent study published in the journal Nature Communications.
“Our ultimate hope is to use blood biopsies to exhaustively search for and characterize even the smallest remnants of tumors,” Viktor Adalsteinsson, PhD, co-first study author and leader of the Blood Biopsy Team at the Broad Institute of MIT and Harvard University, said in a press release.
“And, as tumors evolve in more advanced stages of cancer, developing resistance or becoming metastatic, we might access timepoints that could be pivotal in deciding which therapies are right for that patient.”
While the idea to track cancer by measuring its DNA in the blood is not new, the study, “Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors,” improves many of the tools used to make the method more robust.
The key to tracking tumor properties in blood is the presence of DNA in the bloodstream. When cells die, some of their DNA leaks into the blood. And since tumor DNA differs from that of healthy cells, it potentially can be analyzed.
Up to now, however, the procedure has been hampered by several issues. For instance, a so-called whole-exome analysis requires at least 10 percent tumor DNA in a blood sample. But the amount of tumor DNA can vary widely, researchers said.
Today, it is common to identify tumor DNA by analyzing specific cancer-related genes. But not all tumors carry these specific mutations, making detection of cancer DNA suboptimal. Instead, the team developed a new method, called ichorCNA.
Instead of looking at specific genes, this tool analyzes mutational patterns that are nearly universal in cancer.
Using ichorCNA on 1,439 blood samples collected from 520 patients with metastatic breast or prostate cancer, the team found that between 33 to 49 percent of patients had at least 10 percent cancer DNA in their blood.
“Using cell-free DNA to track cancer is not a new idea, but we’re developing the tools to understand how we can better qualify materials for those types of analyses,” said J. Christopher Love, PhD, one of the senior study authors, and an associate professor of chemical engineering at MIT.
“We’ve established quality metrics to make sure that this technology is cost-effective and scalable for thousands of patients and samples a year,” added Love, who also is a member of the Koch Institute for Integrative Cancer Research at MIT.
In the next step of the study, the team compared the genetic analysis of tumor DNA from blood samples to those performed in tumor tissue. They found that the analyses were well-matched across a range of genetic features.
Importantly, the blood test method is adapted for use in thousands of patients, which is key if it is to be introduced in clinical settings.
“Our study has demonstrated that we can get a cancer whole exome reliably, from blood; that it reflects the matched tumor biopsy; and that it can be done for a significant fraction of patients with metastatic cancer,” said Adalsteinsson.
“This validation suggests that we can use blood biopsies for large-scale genomic characterization of disease in patients with metastatic cancer.”
Gad Getz, PhD, another senior author of the study, underscored that their findings open the door for research that could not have been done earlier.
“The technology will allow us to track the dynamics of cancer and understand the evolution of drug resistance, or the development of the metastatic state, in a way that isn’t possible through surgical biopsies,” said Getz, who is a director of the Cancer Genome Computational Analysis group at Broad. He also is associate professor of Pathology and director of Bioinformatics at the Massachusetts General Hospital Cancer Center.
“With this work, we now have a framework for the precise measurement and quality control of tumor DNA in the plasma, enabling the genomic analysis of blood biopsies with high technical accuracy,” added Matthew Meyerson, MD, PhD, the third senior study author who is an institute member at Broad and professor of pathology at Dana-Farber Cancer Institute and Harvard Medical School.