Diffuse leptomeningeal glioneuronal tumor (DLGNT): a comprehensive clinical and molecular analysis
Year: 2025
Type: article
Study design: Observational Study
Abstract: Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are rare, and optimal treatment remains undefined. We aim to comprehensively characterize their clinical and molecular features, offering granular insights into presentations and therapies to elucidate prognostic factors and therapeutic targets. Histologic, molecular, and clinical data of 30 patients with DLGNT were analyzed. Median age at diagnosis was 7.5 years (range: 0.9-20 years). Disease was localized at diagnosis in 16 patients (53.3%), predominantly in the spinal cord (14/16, 87.5%). KIAA1549::BRAF fusion occurred in 27 (96.4%) of 28 patients. DNA methylation profiling of 23 tumors classified 4 (17.4%) as DLGNT MC-1, 3 (13.0%) as DLGNT MC-2, and 16 (69.6%) as DLGNT, but not to a specific subclass. Median follow-up was 57.5 months. Most patients (90.0%) received adjuvant therapy. Chemotherapy was the first-line adjuvant therapy in 19 patients (70.4%); targeted therapy in 5 patients (18.5%), and radiotherapy in 2 patients (7.4%). Median progression-free survival (PFS) after first chemotherapy, targeted therapy, or radiotherapy was 44 (1-77) months, 18 (4-39) months, and 16.5 (9-23) months, respectively. Five-year PFS was 15.9% ± 8.0, and 5 year overall survival (OS) was 83.3% ± 8.8. Patients older than 9 years at diagnosis (p = 0.002) and those with MC-2 (p = 0.04) had worse 5 year OS. Multi-omic analysis revealed simultaneous activation of multiple signaling pathways, which may serve as potential therapeutic targets. DLGNT remains challenging to treat, with poor outcomes across modalities. Further investigation of treatment, including targeted therapies addressing activated pathways, is needed to improve patient survival.
Source: Acta Neuropathologica
Authors: Margit K. Mikkelsen, Xiaoyu Li, Kaiwen Yu, Anthony A. High, Haiyan Tan, Larissa V. Furtado, Nalin Leelatian, Jessica Bell, Julia D. Berry, Daniel R. Boué, Franklin Chien, Scott L. Coven, Michael C. Dewan, Jason Fangusaro, Jessica B. Foster, Lindsey Hoffman, Julia K. Kofler, Trisha Larkin, Margot Lazow, Adriana May, Bret C. Mobley, Dolly Noun, Benjamin Posorske, Jonathan Schwartz, Ivanna Sheila, Susan Spiller, Ryuma Tanaka, Ibrahim Qaddoumi, Christopher L. Tinkle, Junmin Peng, Giles W. Robinson, Daniel C. Moreira, Jason Chiang
Institutions: St. Jude Children's Research Hospital, Vanderbilt University, Vanderbilt University Medical Center, Novant Health Presbyterian Medical Center, Nationwide Children's Hospital, The Ohio State University, Emory University, Children's Healthcare of Atlanta, Indiana University Health, Indiana University Hospital, Riley Hospital for Children, Indiana University School of Medicine, Children's Hospital of Philadelphia, Phoenix Children's Hospital, University of Pittsburgh, University of Pittsburgh Medical Center, St. Joseph's Children's Hospital, American University of Beirut Medical Center, American University of Beirut, Mayo Clinic, Instituto de Medicina Integral Professor Fernando Figueira, East Tennessee Children's Hospital, Medical College of Wisconsin
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
OpenAlex ID: W4413099696