Individualized blood tests can monitor tumor levels after therapy and determine cancer recurrence


Individualized blood tests can monitor tumor levels after therapy and determine cancer recurrence

Data from the whole genome sequencing of cancer patients have been used to develop individualized blood tests which will probably help doctors tailor patients' treatments, say researchers at Johns Hopkins Kimmel Cancer Center. These new genome-based blood tests may be used to monitor tumor levels after treatment and determine whether the cancer comes back (recurrence).

Victor Velculescu, M.D., Ph.D., associate professor of oncology and co-director of the cancer biology program at Johns Hopkins, said "We believe this is the first application of newer generations of whole-genome sequencing that could be clinically useful for cancer patients. Using this approach, we can develop biomarkers for potentially any cancer patient."

According to an article published in Science Translational Medicine, February 24th issue, the scientists scanned patients' genomes for alterations that, they say, most researchers have not been looking for rearrangements of large chunks of DNA rather than changes in a single DNA letter among billions of others. They call their new approach Personalized Analysis of Rearranged Ends (PARE).

Bert Vogelstein, M.D., Clayton Professor of Oncology, co-director of the Ludwig Institute at Johns Hopkins, and Investigator in the Howard Hughes Medical Institute, said "In sequencing individuals' genomes in the past, we focused on single-letter changes, but in this study, we looked for the swapping of entire sections of the tumor genome. These alterations, like the reordering of chapters of a book, are easier to identify and detect in the blood than single-letter changes."

These types of DNA rearrangements are known to occur only in cancer cells and not in non-cancerous ones, making them perfect biomarkers for cancer.

Using six sets of cancerous and normal tissue samples taken from four colorectal and two breast cancer patients, the team used next-generation sequencing methods to catalogue the genome sequence data of each individual patient. To find DNA rearrangements, the team first identified regions where the number of DNA copies was more or less than anticipated and where sections of different chromosomes fused together. These regions were further analyzed to identify DNA sequences displaying incorrect ordering, orientation, or spacing. A range of four to 15 rearrangements were found in each of the six samples.

They first identified DNA rearrangements in patients' tumor sample, and then looked for the same changes in DNA shed from tumors in the patients' blood. They amplified DNA found in the blood samples of two colorectal cancer patients and determined that these tests were sensitive enough to detect rearranged tumor DNA in these samples.

The scientists say that the results from such blood tests could help doctors detect cancer or its recurrence and inform them on how a patient is responding to cancer treatments. In one colon cancer patient's example, the scientists found a section of chromosome four fused to a section of chromosome eight.

Rebecca Leary, a graduate student at the Johns Hopkins Kimmel Cancer Center, said "We developed a biomarker that could span this rearrangement and used a blood test to evaluate biomarker levels as the patient received a variety of cancer therapies."

Following initial surgery, biomarker levels in patients dropped because the majority of the tumor was removed. The biomarker levels rose again, indicating that additional cancer remained in the patient's body. After chemotherapy and a second surgery, levels of the biomarker dropped significantly, but still showed a small but measurable level of the biomarker. This was consistent with a small metastatic lesion that remained in the patient's liver.

The investigators envision that PARE-based biomarkers could also be used to determine whether cancer cells are present in surgical margins or lymph node tissue removed during surgery and possibly for diagnosing early disease.

Luis Diaz, M.D., assistant professor of oncology at Johns Hopkins, said "Eventually, we believe this type of approach could be used to detect recurrent cancers before they are found by conventional imaging methods, like CT scans."

Velculescu predicts that the technology used to examine the patients' genomes will become inexpensive. He says the genome scan cost them about $5,000 per patient, but that sequencing costs continue to drop. CT scans currently cost $1,500 per scan and are limited in their ability to detect microscopic cancers.

Kenneth W. Kinzler, Ph.D., professor of oncology and co-director of the Ludwig Center at Johns Hopkins, said "If current trends in genome sequencing continue, PARE will be more cost effective than CT scans and could prove to be more informative."

The Johns Hopkins team, who have filed for patents on the technology, say they plan to test more patient samples and to refine their techniques so that a commercially viable genome-based blood test may be achieved.

Under a licensing agreement between the Johns Hopkins University and Genzyme, Velculescu, Vogelstein, and Kinzler, are entitled to a share of royalties received by the University on sales of products related to research described in this paper. The terms of these arrangements are managed by the Johns Hopkins University in accordance with its conflict-of-interest policies.

The National Institutes of Health, The Lustgarten Foundation, the National Colorectal Cancer Research Alliance, and a UNCF-Merck Fellowship funded the research.

Other participants in the research include Isaac Kinde, Frank Diehl and Kerstin Schmidt, from Johns Hopkins; Chris Clouser, Cisilya Duncan, Alena Antipova, Clarence Lee, Kevin McKernan, and Francisco De La Vega from Life Technologies.

Source: Johns Hopkins Medicine

Personalized Blood Tests Monitor Cancer (Video Medical And Professional 2020).

Section Issues On Medicine: Disease