About the Study

The researchers prospectively collected blood and tissue samples from 161 patients with metastatic breast cancer, non-small-cell lung cancer (NSCLC), or castration-resistant prostate cancer. Thirty-seven patients were excluded due to unavailability of the results of the genetic analysis of the tumor or cell-free DNA samples. For 124 evaluable patients for concordance analysis, researchers compared genetic changes in the tumors to those in circulating tumor DNA from the blood samples.


Tumor tissues were analyzed using MSK-IMPACT™, a 410-gene diagnostic test that provides detailed genetic information about a patient's cancer. In each blood sample, the researchers separated the plasma, the liquid part of the blood, from the blood cells. The cell-free DNA extracted from the plasma and, separately, the genome of white blood cells were then sequenced using the high-intensity, 508-gene sequencing assay.

"Finding tumor DNA in the blood is like looking for a needle in a haystack. For every 100 DNA fragments, only one may come from the tumor, and the rest may come from normal cells, mainly bone marrow cells," said Dr. Razavi. "Our combined analysis of cell-free DNA and white blood cell DNA allows for identification of tumor DNA with much higher sensitivity, and deep sequencing also helps us find those rare tumor DNA fragments."

Patients' tumors may have various genetic changes; there can be different changes in different parts of the same tumor, as well as in different sites where the tumor spreads in the body. For these reasons, sequencing over very broad regions of the genome is critically important to identify the multitude and diversity of genetic changes in the tumor.

Key Findings

In 89% of patients, at least one genetic change detected in the tumor was also detected in the blood (97% in metastatic breast cancer patients, 85% in those with NSCLC, and 84% in those with metastatic prostate cancer). Overall, including all genomic variations present in most if not all tumor cells (clonal) as well as those present only in subsets of the cancer cells (subclonal) from tumor tissue, the researchers detected a total of 864 genetic changes in tissue samples across the three tumor types, and 627 (73%) of those were also found in the blood.

Importantly, without any prior knowledge from the analysis of tumor tissue, 76% of "actionable" mutations (genetic changes that can be matched to an approved targeted therapy or one being tested in clinical trials) detected in tissue were also detected in blood.

Pathology Homepage