Press release
Tuesday, August 31, 2021
Type 1 or NF1 neurofibromatosis is the most common cancer predisposition syndrome, affecting 1 in 3,000 people worldwide.
People with an inherited disease known as type 1 or NF1 neurofibromatosis often develop non-cancerous or benign tumors that grow along the nerves. These tumors can sometimes turn into aggressive cancers, but there has been no good way to determine if this transformation has occurred into cancer.
Researchers at the National Cancer Institute’s (NCI) Cancer Research Center, which is part of the National Institutes of Health, and the University of Washington School of Medicine in St. Louis. economic approach to detecting cancer early in people with NF1. Blood tests can also help doctors monitor the good response of patients to the treatment of their cancer.
The findings are published in the August 31 issue of PLOS medicine.
NF1 is the most common cancer predisposition syndrome, affecting 1 in 3,000 people worldwide. The condition, caused by a mutation in a gene called NF1, is almost always diagnosed in childhood. About half of people with NF1 will develop large but benign tumors in the nerves, called plexiform neurofibromas.
In up to 15% of people with plexiform neurofibromas, these benign tumors become an aggressive form of cancer known as a malignant peripheral nerve layer tumor or MPNST. Patients with MPNST have a poor prognosis because the cancer can spread quickly and often becomes resistant to both chemotherapy and radiation. Among people diagnosed with MPNST, 80% die at age five.
“Imagine going through life with a cancer predisposition syndrome like NF1. It’s like a counter-tactile bomb, ”said study co-author Jack F. Shern, MD, a clinical researcher at Lasker in NCI’s pediatric oncology branch.“ Doctors will be on the lookout for cancerous tumors, and you will be watching, but you really want to discover this transformation into cancer as soon as possible. “
Currently, doctors use imaging scans (MRI or PET) or biopsies to determine if plexiform neurofibromas have been transformed into MPNST. However, biopsy findings are not always accurate and the procedure can be extremely painful for patients because tumors grow along the nerves. Image testing, on the other hand, is expensive and can also be inaccurate.
“What we don’t have right now is a tool to help us determine if within this large, bulky benign plexiform neurofibroma, something bad is cooking and is becoming an MPNST,” Dr. Shern said. So we thought, ‘What if we develop a simple blood test where, instead of a whole body MRI or a fantastic PET scan, we could draw a blood tube and say whether or not the patient has MPNST somewhere? “
To achieve this goal, Dr. Shern and his co-directors Aadel A. Chaudhuri, MD, Ph.D., and Angela C. Hirbe, MD, Ph.D., of the Washington University School of Medicine, and their colleagues. Laboratories collected blood samples from 23 people with plexiform neurofibromas, 14 patients with MPNST who had not yet been treated, and 16 healthy people without NF1. Most study participants were adolescents and young adults, the age group in which MPNST most often develops. The researchers isolated cell-free DNA (that is, DNA spilled from cells into blood) from blood samples and used whole-genome sequencing technology to look for differences in the genetic material between the three groups.
Cell-free DNA in patients with MPNST had several characteristics that distinguished it from the DNA of the other two groups. For example, patients with MPNST had pieces of free cell DNA that were shorter than those of people with plexiform neurofibromas or without NF1. In addition, the proportion of cell-free DNA that came from tumors — called the “plasma tumor fraction” —in blood samples was much higher in people with MPNST than in those with plexiform neurofibromas. Together, these differences allowed the researchers to differentiate, with 86% accuracy, between patients with plexiform neurofibromas and those with MPNST.
In the study participants with MPNST, the plasma tumor fraction was also aligned with their good response to treatment. In other words, if their plasma tumor fraction decreased after treatment, the size and number of their tumors (measured by imaging scans) also decreased. An increase in plasma tumor fraction was associated with metastatic recurrence.
“You can imagine treating a patient with a chemotherapy regimen. This blood test could allow us to easily and quickly determine if the disease is decreasing or perhaps even disappearing completely, “Dr. Shern said.” And if I had had surgery and had an MPNST and blood test. blood has been negative, it could be used to monitor the patient forward to see if the tumor returns. “
Dr. Shern noted that one of the limitations of the current study is its small size, although it included people with NF1 from two large hospitals. Researchers plan to conduct a larger trial with more patients. Dr. Shern said the team’s goal is to increase the accuracy of the blood test by 86% to more than 100%. One approach would be to refine genetic analysis to focus on genes that are known to be involved in MPNST.
A simple and economical blood test to detect MPNST early in patients with NF1 would be especially useful in developing countries and other resource-poor areas, where access to equipment and experience required for imaging is limited. , Dr. Shern said.
Such blood tests also have applications in the early detection and control of patients with other genetic disorders that predispose to cancer, such as multiple endocrine neoplasia, in which benign tumors can become cancerous, or Li syndrome. -Fraumeni, which increases the risk of developing various types of cancer.
“This is the perfect opportunity to apply these technologies where we can use a simple blood test to examine a population at risk,” Dr. Shern said. “If the test shows something abnormal, that’s when we know how to act and go look for a tumor.”
The study was supported by NCI’s Intramural Research Program and the National Institute of General Medical Sciences, another part of NIH.
About the Cancer Research Center (CCR): The JRC comprises nearly 250 teams conducting basic, translational, and clinical research in the NCI intramural program, an environment that supports innovative science aimed at improving human health. The CCR clinical program is located at the NIH Clinical Center, the largest hospital in the world dedicated to clinical research. For more information about CCR and its programs, visit ccr.cancer.gov.
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