RT Journal Article
SR Electronic
T1 Imaging Clusters of Pediatric Low-Grade Glioma are Associated with Distinct Molecular Characteristics
JF American Journal of Neuroradiology
JO Am. J. Neuroradiol.
FD American Society of Neuroradiology
SP ajnr.A8699
DO 10.3174/ajnr.A8699
A1 Kazerooni, Anahita Fathi
A1 Kraya, Adam
A1 Rathi, Komal S.
A1 Kim, Meen Chul
A1 Kesherwani, Varun
A1 Corbett, Ryan
A1 Vossough, Arastoo
A1 Khalili, Nastaran
A1 Gandhi, Deep
A1 Familiar, Neda Khalili Ariana M.
A1 Jin, Run
A1 Huang, Xiaoyan
A1 Zhu, Yuankun
A1 Sickler, Alex
A1 Lueder, Matthew R.
A1 Phul, Saksham
A1 Storm, Phillip B.
A1 Ware, Jeffrey B.
A1 Foster, Jessica B.
A1 Mueller, Sabine
A1 Rokita, Jo Lynne
A1 Fisher, Michael J.
A1 Resnick, Adam C.
A1 Nabavizadeh, Ali
YR 2025
UL http://www.ajnr.org/content/early/2025/02/14/ajnr.A8699.abstract
AB BACKGROUND AND PURPOSE: Cancers show heterogeneity at various levels, from genome to radiological imaging. This study aimed to explore the interplay between genomic, transcriptomic, and radiophenotypic data in pediatric low-grade glioma (pLGG), the most common group of brain tumors in children.MATERIALS AND METHODS: We analyzed data from 201 pLGG patients in the Children’s Brain Tumor Network (CBTN), using principal component analysis and K-Means clustering on 881 radiomic features, along with clinical variables (age, sex, tumor location), to identify imaging clusters and examine their association with 2021 WHO pLGG classifications. To determine the transcriptome pathways linked to imaging clusters, we employed a supervised machine learning model with elastic net logistic regression based on the pathways identified through gene set enrichment and gene co-expression network analyses.RESULTS: Three imaging clusters with distinct radiomic characteristics were identified. BRAF V600E mutations were primarily found in imaging cluster 3, while KIAA1549::BRAF fusion occurred in subtype 1. The model's predictive accuracy (AUC) was 0.77 for subtype 1, 0.78 for subtype 2, and 0.70 for subtype 3. Each imaging cluster exhibited unique molecular mechanisms: subtype 1 was linked to oxidative phosphorylation, PDGFRB, and interleukin signaling, whereas subtype 3 was associated with histone acetylation and DNA methylation pathways, related to BRAF V600E pLGGs.CONCLUSIONS: Our radiogenomics study indicates that the intrinsic molecular characteristics of tumors correlate with distinct imaging subgroups in pLGG, paving the way for future multi-modal investigations that may enhance understanding of disease progression and targetability.ABBREVIATIONS: WHO = World Health Organization; CBTN = Children’s Brain Tumor Network; pLGG = pediatric Low-Grade Glioma; EFS = Event-Free Survival; PC = Principal Component; CNS = Central Nervous System.