CDC42BPA::BRAF Represents a Novel Fusion in Desmoplastic Infantile Ganglioglioma/Desmoplastic Infantile Astrocytoma

Abstract

Summary Desmoplastic infantile ganglioglioma/desmoplastic infantile astrocytoma (DIG/DIA) are low-grade glial/glioneuronal tumors occurring predominantly in the cerebral hemispheres of infants. DIG/DIA exhibit BRAF or RAF1 alterations leading to oncogenic mitogen-activated protein kinase (MAPK) pathway activation. Here, we report the discovery of the novel CDC42BPA::BRAF fusion in a three-month-old patient with left frontotemporal DIA using DNA sequencing. Independent validation was performed through RNA sequencing. This fusion joins the kinase domains of BRAF and CDC42BPA, potentially constitutively activating both. It marks the first report of a fusion involving the actomyosin regulatory kinase CDC42BPA/MRCKα in brain tumors, suggesting potential involvement of actin remodeling defects in DIG/DIA. Surgical excision is curative for DIG/DIA, but incomplete resection, recurrence, malignant transformation, or metastases may necessitate adjuvant chemotherapy, posing risks. Identifying and excluding molecular alterations is crucial for selecting targeted therapies, such as BRAF and MEK inhibitors. These options present potential treatments with lower toxicity compared to conventional chemotherapy.