Rethinking FOXR2 Activation in Brain Tumors: A Breakthrough in Diagnosis and Care

The world of medicine is abuzz with a groundbreaking discovery that challenges the long-held assumption about the genetic marker FOXR2. For years, physicians have relied on this marker to diagnose central nervous system (CNS) neuroblastoma, a type of brain tumor. However, new research from St. Jude Children’s Research Hospital reveals that FOXR2 activation is not exclusive to CNS neuroblastoma. In fact, it was found in multiple pediatric CNS tumor types, including brain tumors, with significantly different clinical outcomes.

According to Dr. Jason Cheng-Hsuan Chiang, corresponding author of the study, “People have been using FOXR2 activation as a clinical diagnostic for CNS neuroblastoma. But we unexpectedly saw it in a patient’s recurrent non-neuroblastoma tumor, which motivated us to look into other brain tumors.” The researchers used data from the St. Jude Cloud, a vast repository of genomic and sequencing data from St. Jude patients, to identify 42 tumors with activated FOXR2 in 41 patients.

The findings were published today in Neuro-Oncology, a journal of the Society for Neuro-Oncology. “When we looked at the clinical outcomes of the different types of tumors with FOXR2 activation, there was a pretty stark difference,” said co-first author Emily Hanzlik, MD. “The CNS neuroblastomas had an exceptionally good outcome when they were treated with multimodal therapy, whereas the other types of tumors in the cohort, the high-grade gliomas and the pineoblastomas, had pretty dismal outcomes.”

This study highlights the importance of combining molecular findings like DNA and RNA sequencing, histology, and imaging to correctly understand a specific brain tumor. “Only with a holistic view can we choose the best treatment approach for that patient,” Dr. Chiang emphasized.

The discovery of undetected mechanisms of FOXR2 activation in multiple brain tumor types has significant implications for diagnosis, prognosis, and treatment. As Dr. Alexa Siskar, co-first author, noted, “Now that we described these genomic events, hopefully, others will be able to detect them in their patients as well.” This breakthrough opens up new avenues for research and care, ultimately leading to better outcomes for brain tumor patients.