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New Approach Highlights Potential for Liquid Biopsies

By Ryan Bushey | November 6, 2017

Researchers have developed a new method for making “blood biopsies” for cancer more effective by using whole exome sequencing to monitor tumor DNA from blood samples. Image: Susanna Hamilton

A new study could bring the prospects of liquid biopsies one step closer to reality.

Researchers hailing from the Massachusetts Institute of Technology, Dana-Farber Cancer Institute (DFCI), and the Massachusetts General Hospital used whole exome sequencing to demonstrate that almost 90 percent of a tumor’s genetic features can be detected in blood samples. 

Furthermore, the study indicated this approach could be effectively applied in up to 49 percent of patients with advanced forms of breast and prostate cancer.

Here’s how this experiment worked.

First, the team developed an “unbiased approach” for detecting and measuring levels of cancer DNA before shifting into the whole-exome sequencing phase. 

Building a whole exome from DNA fragments currently requires at least 10 percent tumor DNA in a blood sample, but that fraction of DNA can vary wildly from patient to patient. Most blood biopsy methods search for tumor DNA by screening for mutations in known cancer-related genes, but this targeted approach misses cancers without those mutations.

This fact led the team to develop a new tool call ichorCNA, which was able to analyze DNA fragments for mutation patterns nearly universal in cancer genomes.

Next, the scientists tested and refine ichorCNA on 1,439 blood samples that were collected from 520 metastatic breast or prostate cancer patients.

This approach found that in 33 to 49 percent of the metastatic breast and prostate cancer patients samples that tumor DNA was comprised of greater than 10 percent of the cell-free DNA in their blood warranting the feasibility of whole-exome sequencing.

Finally, they compared surgically obtained tumor biopsies to data collected from whole-exome sequencing of cell-free DNA from a group of 41 patients. Findings had shown there was significant matching across a number of genetic features like clonal somatic mutations and copy number alterations between the two groups.

“Our ultimate hope is to use blood biopsies to exhaustively search for and characterize even the smallest remnants of tumors,” said Viktor Adalsteinsson, co-first author on the paper and group leader at the Broad Institute, in a statement. “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.”

The next phase of research for this experiment will involve an expanded collaboration that could lead to comprehensive mapping of metastatic and drug-resistant tumors from blood samples at scale.

Ultimately, a functional liquid biopsy could provide a less invasive alternative to diagnosing these diseases. Other applications for this technology could include enhanced methods to monitor treatment responses, watch for recurrence, increase the resolution with which clinicians can understand metastatic cancer, and increase accessibility to precision medicine approaches.

The study was published in the journal Nature Communications.

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