A major breakthrough in nature! Develop a new blood test based on DNA packaging to detect multiple cancers!

June 4, 2019 / Biovalley BIOON / - researchers at Kimmel Cancer Center of Johns Hopkins University have developed a simple new blood detection method, which can detect the presence of seven different types of cancer by discovering the unique pattern of DNA fragments shed by cancer cells circulating in the blood In this proof of concept study, the test called delfi (DNA evaluation of fragments for early understanding) accurately detected the presence of cancer DNA in blood samples of 57% to more than 99% of patients, including 208 patients with different stages of breast cancer, colorectal cancer, lung cancer, ovarian cancer, pancreatic cancer, stomach or bile duct cancer in the United States, Denmark and the Netherlands Delfi also performed well in blood samples from 215 healthy people, with only 4 misdiagnosed as cancer The test uses machine learning to identify abnormal patterns of DNA fragments in the blood of cancer patients By studying these patterns, researchers say, they can determine the origin of cancer tissue in as many as 75% of cases The study was recently published in nature Source: Professor of oncology, joint director of cancer biology program, and research correspondent Victor E Dr Velculescu said blood tests for cancer tests, or so-called "liquid biopsies," usually look for mutations, changes in DNA sequences within cancer cells, or for methylation, the chemical reaction of adding a methyl group to DNA But not all cancer patients have changes that can be detected by these methods, so there is still a lot of room for improvement in early detection methods of cancer Delfi uses a different approach, he said, by looking at the size and quantity of DNA from different regions of the genome in the blood, to study the way DNA is packaged in the nucleus to find clues to such packaging Dr Alessandro leal is one of the lead authors of the study and a PhD student at the Johns Hopkins University School of medicine He explained that the nucleus of healthy cells wraps the DNA like a well-organized suitcase, with different regions of the genome carefully placed in different compartments In contrast, the nucleus of cancer cells is more like a disordered suitcase, with the contents of the genome thrown in at random "For various reasons, the cancer genome is disordered in the way it is packaged, which means that when cancer cells die, they release DNA into the blood in a disordered way," said Dr Jillian phallen, lead author of the study and postdoctoral fellow at the Johns Hopkins Kimmel Cancer Center "By detecting this cell-free DNA (cfdna), delfi can help identify the presence of cancer by detecting abnormalities in the size and quantity of DNA in different regions of the genome, which is based on DNA packaging "The researchers warn that the potential of this test must be further validated in more studies, but if it is further validated, it can be used to screen for cancer by taking a tube of blood from a person, extracting cfdna, studying its gene sequence, and determining the fragment structure of cfdna The whole genome fragment pattern from an individual can then be compared with a reference population to determine whether the pattern is healthy or cancer derived Dr Robert B scharpf, senior author and associate professor of oncology of the study, said that because genome-wide differentiation patterns may reveal differences associated with specific tissues, they can also indicate sources of cancer, such as breast, colon and lung cancer, when they originate from cancer Delfi analyzes millions of sequences from hundreds to thousands of regions in the genome at the same time to identify tumor specific abnormalities from the small amount of cfdna Using delfi, the researchers found that the whole genome cfdna fragment spectrum of cancer patients and healthy individuals was different Stephen Cristiano, the lead author of the study, said that the division pattern of cfdna in cancer patients appeared to be derived from a mixture of DNA released from blood and tumor cells, and showed the increase and decrease of the size of multiple different genomic differences in different regions In the current study, Johns Hopkins University researchers and colleagues from some institutions in the United States cooperated to sequence the cfdna of 208 cancer patients with low coverage whole genome, including 54 cases of breast cancer, 27 cases of colorectal cancer, 12 cases of lung cancer, 28 cases of ovarian cancer, 34 cases of pancreatic cancer, 27 cases of gastric cancer, 26 cases of cholangiocarcinoma They also sequenced the entire genome and analyzed the cfdna of 215 healthy individuals Samples of all cancer patients were obtained before any treatment was performed, most of them (183) were from people who could treat the disease by surgically removing the tumor In general, the researchers say that healthy individuals have similar debris characteristics, while cancer patients have more variable debris characteristics and are unlikely to match healthy characteristics Delfi detected cancer in 73% of cancer patients and misclassified 4 of 215 healthy individuals (98% specificity) The detection also found that the accuracy rate in determining the tissue source of cfdna was 61% - 75% Combining delfi with mutation based cfdna analysis, researchers can accurately detect 91% of cancer patients Velculescu, Leal, phallen, scharpf, Cristiano and their colleagues are expanding their analysis to study delfi's performance in thousands of samples "We are encouraged by the potential of delfi because it studies a completely independent set of cell-free DNA features that have been difficult for patients for many years," Velculescu said We look forward to working with partners around the world to make this test available to patients "Because the test is easy to manage and uses simple and inexpensive laboratory methods, Velculescu expects that the test may ultimately be more cost-effective than other cancer screening tests, including other current cfdna tests Reference: Victor E Velculescu et al Genome wide cell free DNA fragmentation in patients with cancer, nature (2019) Doi: 10.1038/s41586-019-1272-6