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Press release
Tuesday, August 31, 2021
Type 1 neurofibromatosis, or NF1, is the most common cancer predisposition syndrome, affecting 1 in 3,000 people worldwide.
People with an inherited disease known as neurofibromatosis type 1 or NF1 often develop non-cancerous or benign tumors that grow along the nerves. These tumors can sometimes turn into aggressive cancers, but there hasn’t been a good way to determine if this transformation into cancer has occurred.
Researchers at the National Cancer Institute (NCI) Center for Cancer Research, part of the National Institutes of Health, and the Washington University School of Medicine in St. Louis have developed a blood test that they believe could one day offer a highly sensitive and inexpensive approach to detect cancer early in people with NF1. The blood test could also help doctors monitor how well patients are responding to treatment for their cancer.
The results 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 on the nerves called plexiform neurofibromas.
In up to 15% of people with plexiform neurofibromas, these benign tumors develop into an aggressive form of cancer known as a peripheral nerve sheath malignancy, or MPNST. Patients with MPNST have a poor prognosis because the cancer can spread quickly and often becomes resistant to both chemotherapy and radiation therapy. Of those diagnosed with MPNST, 80% die within five years.
“Imagine living with a cancer predisposition syndrome like NF1. It’s kind of like a ticking time bomb, ”said study co-author Jack F. Shern, MD, a Lasker clinical researcher in the pediatric oncology branch of NCI. “Doctors are going to be watching for cancerous tumors, and you’re going to be watching them, but you really want to find out about this transformation into cancer sooner rather than later.”
Doctors currently use either imaging tests (MRI or PET) or biopsies to determine if the plexiform neurofibromas have turned into MPNST. However, the results of the biopsy are not always accurate and the procedure can be extremely painful for patients as the tumors grow along the nerves. Imaging tests, on the other hand, are expensive and can also be inaccurate.
“What we don’t have right now is a tool to help us determine if in this large, bulky benign plexiform neurofibroma, something bad is simmering up and turning into an MPNST,” Dr Shern said. . “So we thought, ‘What if we developed a simple blood test where, instead of a whole body MRI or a fancy PET scan, we could just take a tube of blood and say whether or not the patient has one. MPNST somewhere? “”
In pursuit of this goal, Dr Shern and study co-leads Aadel A. Chaudhuri, MD, Ph.D., and Angela C. Hirbe, MD, Ph.D., from the Washington University School of Medicine, and their collaborators collected blood samples from 23 people with plexiform neurofibromas, 14 patients with untreated MPNST, and 16 healthy people without NF1. Most of the study participants were adolescents and young adults, the age group in which MPNST most commonly develops. Researchers isolated cell-free DNA – that is, DNA released from cells into the bloodstream – from blood samples and used whole genome sequencing technology to look for differences in genetic material. between the three groups.
Cell-free DNA in patients with MPNST exhibited several characteristics that set it apart from DNA in the other two groups. For example, patients with MPNST had pieces of cell-free DNA that were shorter than those in people with plexiform neurofibromas or without NF1. In addition, the proportion of cell-free DNA from tumors – called “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 study participants with MPNST, the plasma tumor fraction was also consistent with their response to treatment. In other words, if their plasma tumor fraction decreased after treatment, the size and number of their tumors (as measured by imaging scans) also decreased. An increase in the plasma tumor fraction was associated with metastatic recurrence.
“You can imagine treating a patient with a regimen of chemotherapy. This blood test could easily and quickly allow us to determine if the disease is getting better or maybe even going away completely, ”said Dr Shern. “And if you had had surgery and taken an MPNST, and the blood test was negative, you could use it to monitor the patient in the future to see if the tumor comes back.”
Dr Shern noted that one of the limitations of the current study is its small size, even though it included people with NF1 from two large hospitals. The 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 from 86% to almost 100%. One approach would be to refine the genetic analysis to focus on genes known to be involved in MPNST.
A simple and inexpensive blood test to detect MPNST early in patients with NF1 would be particularly useful in developing countries and other low-resource regions, where access to the equipment and expertise necessary to performing imaging is limited, said Dr Shern.
Blood tests of this type also have applications in the early detection and monitoring of patients with other genetic disorders predisposing to cancer, such as multiple endocrine neoplasia, in which benign tumors can become cancerous, or Li syndrome. -Fraumeni, which increases the risk of developing several types of cancer.
“This is the perfect opportunity to apply these technologies where we can use a simple blood test to screen for a population at risk,” said Dr Shern. “If the test shows anything abnormal, that’s when we know how to act and look for a tumor.
The study was supported by the NCI intramural research program and the National Institute of General Medical Sciences, another part of the NIH.
About the Cancer Research Center (CCR): The CCR comprises nearly 250 teams conducting fundamental, translational and clinical research in the NCI intramural program, an environment supporting innovative science aimed at improving human health. The CCR clinical program is housed at the NIH Clinical Center, the world’s largest hospital dedicated to clinical research. For more information about CCR and its programs, visit ccr.cancer.gov.
About the National Cancer Institute (NCI): The NCI leads the National Cancer Control Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families through cancer prevention and biology research, the development of new interventions and training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call the NCI contact center, Cancer Information Service, at 1-800-4-CANCER (1-800 -422-6237).
About the National Institutes of Health (NIH):The NIH, the national agency for medical research, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the principal federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.
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