Cancer is caused, generally, by genetic mutations starting in individual cells. A mutation changes how the body’s cells work, which can cause cells to multiply uncontrollably. Cancer typically requires multiple gene mutations.

For the past several decades, scientists have been investigating the genetics of cancer and have identified many tumor-specific genetic markers. These tumor-specific markers are used to diagnose cancer and, in many cases, help doctors predict the behavior of the cancer and a patient’s prognosis.

Here are two research projects donors made possible that are looking at novel ways to use genetic markers of the disease to improve treatment and outcomes for kids with cancer:

Cell-Free DNA Testing

Cell-free DNA (cfDNA) screening is offering new promise for cancer diagnosis and treatment. You may be familiar with prenatal testing that screens a pregnant person’s blood to determine if the baby is more likely to have a genetic disorder such as Down Syndrome.

Using similar cfDNA screening, doctors can test a patient’s cerebrospinal fluid and blood for genetic markers of their cancer.

H3K27M is a genetic mutation found in DIPG (diffuse intrinsic pontine glioma) and DMG (diffuse midline glioma), two deadly forms of pediatric brain cancer.

Finding the H3K27M genetic marker using cfDNA screening helps predict how well a patient’s tumor is responding to treatment and when/if the tumor is going to recur. Importantly, cfDNA screening results can be more predictive than MRI, where it is often difficult to distinguish between tumor growth and inflammation related to treatment.

Adam Green, MD is the chair of a Phase 1/2 clinical trial for pediatric high-grade glioma, including DIPG and DMG. The trial opened in May 2022 and will enroll 150-200 patients across more than 200 institutions in the United States, Canada, and Oceania.

Dr. Green and his research team will conduct cfDNA testing on cerebrospinal fluid and/or blood samples from a set of patients upon their enrollment in the trial, after radiation treatment, and every three months to follow.

From these patient samples, researchers will gain a better understanding of optimal cfDNA screening techniques, how cfDNA levels predict spread of the cancer, and if results correlate with or perform better than MRI findings.

The preliminary data gathered from this work will be necessary to show value in conducting this testing on all remaining patients enrolled on the clinical trial. Those results will have a major impact on how pediatric high-grade gliomas are diagnosed in the future without need for a biopsy and in predicting recurrence and modifying treatment to improve outcomes for kids with high-grade glioma.

Analysis of Stem Cell Transplant Process

Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant pediatric brain tumor that is found predominantly in very young children who are often too young to receive radiation treatment.

For a child with ATRT who is too young for radiation, their stem cells are collected before they begin high-dose chemotherapy. After the patient has completed high-dose chemotherapy treatment, s/he receives an autologous stem cell transplant of their previously collected stem cells. The transplant, known as an autologous peripheral blood stem cell (PBSC) rescue, helps replace stem cells that were destroyed by the high-dose chemotherapy treatment.

Treating ATRT in young children using high-dose chemotherapy and stem cell rescue has increased survival rates. But additional research is needed to understand if this process can be further improved.

Jean Mulcahy Levy, MD runs transplants in the Center for Cancer and Blood Disorders at Children’s Hospital Colorado. CD34 is a stem cell marker for ATRT. During PBSC collection for ATRT patients, CD34 peripheral stem cells are removed from the blood and the remaining components (plasma, white cells/platelets, and red cells) are returned to the patient.

Dr. Mulcahy Levy, along with Anandani Nellan, MD, MPH from the NCI’s Center for Cancer Research and Siddhartha Mitra, PhD, will evaluate available CD34 stem cell samples from patients who were previously treated at Children’s Colorado.

The researchers will work to identify any isolated ATRT tumor cells in the samples using immunofluorescence. If ATRT tumor cells are identified, researchers will determine the amount and then will begin developing methods to remove the cancer cells.

This is the first work of its kind to understand if the treatment of ATRT in young children can be made safer and more effective. This project has the potential to improve the treatment provided to kids with ATRT and increase their survival.

Thanks to generous donors, doctors and researchers in The Morgan Adams Foundation Pediatric Brain Tumor Research Program are using genetic markers to find new and better ways to treat kids with cancer.