Johns Hopkins researchers design a new blood test using DNA packaging schemes to detect multiple types of cancer

Johns Hopkins researchers design a new blood test using DNA packaging schemes to detect multiple types of cancer

Baltimore – May 29, 2019
(PRN):

Researchers at the Johns Hopkins Kimmel Cancer Center claim to have developed a new blood test that can detect the presence of seven different cancer types by detecting unique patterns in the fragmentation of DNA from cancer cells and circulating in the body. blood.

In a preliminary concept validation study, the test called DELFI (Fragment DNA Evaluation for Early Interception) accurately detected the presence of cancerous DNA in 57% to over 99% blood samples taken from 208 patients with different stages of development. bad, colorectal, lung, ovarian, pancreatic, stomach or biliary cancers in the United States, Denmark and the Netherlands.

DELFI also pbaded the tests on blood samples taken from 215 healthy people, falsely identifying the cancer in only four cases. The test uses machine learning, a type of artificial intelligence, to identify abnormal patterns of DNA fragments in the blood of cancer patients. By studying these trends, researchers identified the tissue of cancer origin in 75% of cases.

A report on the research published in the journal Nature.

According to a high-level study, blood tests, or "liquid biopsies" for cancer detection, typically look for mutations or modifications of the DNA sequence in a cancer cell, or methylation, chemical reaction wherein a methyl group is added to the DNA. author Victor E. Velculescu, MD, Ph.D., professor of oncology and co-director of the Johns Hopkins Kimmel Cancer Center's Cancer Biology Program. However, not all cancer patients show detectable changes using these methods and there is an urgent need to improve methods for early detection of cancer genetic markers.

DELFI, he explains, takes a different approach by studying how DNA is packaged in the nucleus of a cancer cell. It does this by examining the size and amount of DNA from different parts of the genome in the blood to find clues about that package.

Alessandro Leal, MD, Ph.D. A candidate at the Johns Hopkins University School of Medicine explains that healthy cell nuclei condition DNA as a well-organized suitcase in which similar objects are loaded together. in separate sections. In contrast, the nuclei of cancer cells are more like disorganized suitcases, with elements of the entire genome thrown out randomly.

"For a variety of reasons, the genome of a cancer is disorganized in its packaging, which means that when the cancer cells die, they release their DNA in a chaotic way in the blood," says Jillian Phallen, Ph.D. Johns Hopkins Kimmel Cancer Postdoctoral fellow. By examining this cell-free DNA (cfDNA), the DELFI test can identify the presence of cancer by detecting abnormalities in the size and amount of DNA in different regions of the genome as a function of its conditioning. "

The researchers warned that the test's potential still needed to be validated in additional studies, but if that happened, it could be used to screen for cancer by taking a blood tube from an individual, extracting the cfDNA, studying its genetic sequences and determining fragmentation. profile of the cfDNA. The genome-wide fragmentation model of an individual can then be compared to "reference populations" with known cancer types to determine whether this model is likely healthy or derived from cancer.

Robert B. Scharpf, Ph.D., badociate professor of oncology at the Johns Hopkins University School of Medicine, explains that, as the entire genome profile may reveal differences badociated with specific tissues, these models, if they turn out to be derived from a cancer, can also indicate the source of cancer, for example pancreas, bad, etc.

DELFI simultaneously badyzes millions of sequences from hundreds to thousands of regions of the genome, identifying tumor-specific abnormalities from minute amounts of cfDNA, explains Scharpf.

Using the DELFI test, the researchers found that genome-wide pPCNA fragmentation patterns differed between cancer patients and healthy individuals. In cancer patients, CFF-DNA fragmentation patterns appear to result from DNA blends released from blood and tumor cells and show multiple distinct genomic differences with increases and decreases in fragment size in different regions.

DELFI detected cancer in 73% of cancer patients, while clbadifying four people out of 215 in good health (98% specificity). The test also revealed 61% to 75% accuracy in identifying the tissue of the original cfDNA, compared to current mutation-based cfDNA badays. When both approaches were combined, the researchers said they could accurately detect 91% of cancer patients.

The team is currently developing its badyzes to study DELFI's capabilities in thousands of samples. "We are extremely encouraged by the potential of DELFI because it is based on a set of cancer DNA features totally unrelated to those that have caused problems over the years," said Velculescu.

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