Pediatric spinal glioma tumor gene alterations hint at therapeutic target
Researchers studied data from 17 children with spinal HGGs
Tumors in children with aggressive gliomas that formed in the spinal cord all exhibited genetic changes that might be able to be targeted therapeutically, a study shows.
Molecular profiling of the tumor tissue showed that many changes in these rare tumors were similar to when gliomas form in the brain.
“The study presented here contributes to a better understanding of spinal [pediatric high-grade glioma] and thus to improving treatment strategies and potential prognosis for the affected patients,” the researchers wrote. The study, “Pediatric spinal high-grade glioma in the pediatric precision oncology registry INFORM: Identification of potential therapeutic targets,” was published in Neuro-Oncology Advances.
Gliomas originate in glia, the support cells of the central nervous system (CNS), which includes the brain and spinal cord. The tumors can form in either place, but they’re more common in the brain. They can be categorized as low grade or high grade, based on how abnormal the cancer cells look under a microscope and how likely they are to spread and invade healthy tissue. High-grade tumors are more aggressive and faster growing.
High-grade gliomas (HGG) of the spine are rare, especially in children, and are associated with a poor prognosis. Treatment usually involves surgery to remove as much of the tumor as possible to ease symptoms, but data on the optimal treatment approach are limited.
In recent years, genetic analyses have enabled scientists to learn more about the molecular characteristics of pediatric brain gliomas. Such studies in spinal gliomas are lacking, however, but understanding them better could lead to more targeted treatment approaches being developed.
Studying spinal HGGs
Here, a team led by researchers in Germany sought to learn more about the genetic features of spinal HGGs and their clinical effects in children and examined data from 17 children diagnosed with spinal HGGs who were participating in the Individualized Therapy For Relapsed Malignancies in Childhood (INFORM) registry. The INFORM registry is an ongoing, international, multicenter, molecular diagnostic study of pediatric patients with aggressive cancers. The children were enrolled at registry sites in Germany, Norway, and Sweden between January 2015 and October 2023.
While all 17 tumors were originally classified as high-grade based on microscopic tissue analysis, molecular analyses indicated that only 12 exhibited clear features of a high-grade nature. Two others had features of being low-grade and three couldn’t be definitively classified.
The finding “underlines the importance of molecular diagnostics” for characterizing gliomas,” the researchers wrote.
Also, a number of genetic alterations usually seen in high-grade brain gliomas was also found in these spinal tumors.
“We show that the assignment of these tumors to one of the molecular HGG subgroups is possible in most cases,” and that “genetic alterations do not differ remarkably between molecular” spinal and brain pediatric HGG, wrote the researchers, who said in all 12 cases of molecularly confirmed HGG, “at least one alteration was identified that could serve as a direct target or provide rationale for targeted therapy approaches.”
Genetic changes in high-grade spinal gliomas
Eight of the tumors — two-thirds of the group with molecularly confirmed HGGs — had the K27M mutation on the H3F3A gene, which is consistent with an aggressive glioma type called diffuse midline glioma.
Mutations in the TP53 gene were also detected in eight tumors (47.1%), while mutations in the ATRX gene were detected in four (23.5%).
A frequently altered targetable gene was FGFR1, with mutations detected in one-quarter of molecularly confirmed HGGs. Some case reports have suggested that medications that suppress FGFR1 and related proteins could have anti-tumor activity in pediatric gliomas with mutations in this gene.
All 12 children with molecularly confirmed HGG had undergone surgical treatment and some also received various combinations of chemotherapy or radiation. Four children received targeted therapy based on results from the molecular tumor analysis.
Unlike traditional chemotherapies that indiscriminately affect fast-growing cells, targeted therapies are designed to hone in on specific molecular and genetic changes that tumor cells use to survive. To be eligible for such a treatment, molecular analyses must confirm the patient’s tumor does indeed have that specific characteristic targeted by the therapy.
Of the 12 children with molecularly confirmed high-grade glioma, nine died a median of 20.5 months after their diagnosis.
Given that the study involved a small number of patients, no conclusions could be definitively drawn on optimal treatment approaches for this aggressive type of pediatric tumor.
“Considering the fatal outcome of this disease, novel treatment approaches are needed and therefore investigations of larger [groups] of … patients are required,” the researchers wrote.
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