Diffuse leptomeningeal glioneuronal tumour (DLGNT) in children: the emerging role of genomic analysis

• Published in: Acta neuropathologica communications Vol. 9; no. 1; p. 147
• Main Authors: Manoharan, Neevika, Ajuyah, Pamela, Senapati, Akanksha, Wong, Marie, Mullins, Anna, Rodriguez, Michael, Doyle, Helen, McCowage, Geoff, Lau, Loretta M S, Ekert, Paul G, Ziegler, David S
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07-09-2021; BioMed Central; BMC
• Subjects: Adolescent; Analysis; Antineoplastic Agents - therapeutic use; Binding sites; Biopsy; Brain Neoplasms - diagnosis; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain tumors; Brain tumour; Cancer; Carboplatin; Case Report; Child; Childhood malignancy; Chromosomes; Diffuse leptomeningeal glioneuronal tumour; DNA methylation; Female; Genomes; Genomics - methods; Histopathology; Humans; Immunohistochemistry; Kinases; Male; Meningeal Neoplasms - diagnosis; Meningeal Neoplasms - drug therapy; Meningeal Neoplasms - genetics; Meningioma - diagnosis; Meningioma - drug therapy; Meningioma - genetics; Mutation; Nervous system; Paediatrics; Proteins; Rare diseases; Spinal cord; Spinal Cord Neoplasms - diagnosis; Spinal Cord Neoplasms - drug therapy; Spinal Cord Neoplasms - genetics; Tumors; Vincristine; Diffuse leptomeningeal glioneuronal tumour; Brain tumour; Paediatrics; Childhood malignancy
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-021-01248-w

Diffuse leptomeningeal glioneuronal tumours (DLGNT) represent rare enigmatic CNS tumours of childhood. Most patients with this disease share common radiological and histopathological features but the clinical course of this disease is variable. A radiological hallmark of this disease is widespread leptomeningeal enhancement that may involve the entire neuroaxis with predilection for the posterior fossa and spine. The classic pathologic features include low- to moderate-density cellular lesions with OLIG2 expression and evidence of 'oligodendroglioma-like' appearance. The MAPK/ERK signaling pathway has recently been reported as a potential driver of tumourigenesis in up to 80% of DLGNT with KIAA1549:BRAF fusions being the most common event seen. Until now, limited analysis of the biological drivers of tumourigenesis has been undertaken via targeted profiling, chromosomal analysis and immunohistochemistry. Our study represents the first examples of comprehensive genomic sequencing in DLGNT and shows that it is not only feasible but crucial to our understanding of this rare disease. Moreover, we demonstrate that DLGNT may be more genomically complex than single-event MAPK/ERK signaling pathway tumours.