Abstract

Abstract INTRODUCTION Genome-wide DNA methylation profiling is performed for pediatric low-grade glioma (pLGG) with diagnostic challenge. We compared histological diagnosis, DNA methylation profiling and integrated diagnosis for pLGG. METHODS We analyzed histology, molecular findings, DNA methylation profiling and integrated diagnosis of pLGG that were registered to the central diagnosis of Japan Children’s Cancer Group from March 2018 to June 2024 and underwent genome-wide DNA methylation profiling. RESULTS Fifty-eight cases were enrolled. Thirty-seven cases (64%) had calibrated scores of 0.84 or higher (match), and 21 cases (36%) had the scores below 0.84 (no match). Definitive diagnoses based on integrated diagnoses were achieved in 22 cases (59%) among the match cases, in 6 cases among the no match cases and in total 28 cases (48%). Tumor types of the 28 cases with definitive diagnoses were pilocytic astrocytoma (PA) in 16 cases, diffuse low-grade glioma, MAPK pathway-altered in 2 cases, subependymal giant cell astrocytoma in 2 cases, dysembryoplastic neuroepithelial tumour in 2 cases, and others in 6 cases. All 6 cases with definitive diagnoses among the no match cases were PA. Discrepancies between histological diagnosis and methylation class were observed in total 34 cases (match 17 cases, no match 17 cases). Among the 34 cases, definitive diagnoses were achieved in 8 cases (match 6 cases, no match 2 cases) and all the diagnoses supported the histological diagnoses. Twenty-one cases of the 34 cases were histologically diagnosed with unspecific tumor types like low-grade glioma or classified to MC Control tissue in DNA methylation profiling. DISCUSSION/CONCLUSION Genome-wide DNA methylation profiling was useful for pLGG matched to specific methylation class. Sixteen percents of the match cases showed discrepancy between histological diagnoses and methylation class, but supported histological diagnoses as definitive diagnoses, indicating the importance of integrated diagnosis.