Abstract Background WNT-activated medulloblastoma (WNT-MB) are uncommon, and report on relevant clinical experience is lacking from Asia. In this study, we report our experience in managing children with WNT-MB at a tertiary referral center in Beijing, China. Methods A retrospective analysis was conducted on 87 patients with WNT-MB managed at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2016 to July 2025. Patient demographics, histopathological and molecular, treatment, and survival data were collected. WNT-MB was confirmed by histopathology (classic histology) and molecular profiling (CTNNB1/APC-mutant, and/or subgrouping by methylation array). Results Among the study cohort, male to female ratio was 1.02,and median age was 9.2 years (3.41-16.7); 9 patients (10.3%) had metastasis. Seventy-six patients had gross-total resection, 10 near-total resection, and one subtotal resection. Where sequenced, 82 patients had tumor with CTNNB1 mutation and 1 had APC mutation. Sixty-six tumors were TP53 wild-type and 18 carried pathogenic TP53 variants. Only one of TP53 mutant tumors was metastatic at diagnosis. All patients received adjuvant craniospinal irradiation (CSI) and chemotherapy. The median CSI dose was 23.4 Gy (23.4-39.6), and tumor-bed total dose 54 Gy (54-55.8). At median follow-up of 4.62 years (1.02-9.57), 10 patients relapsed, and one died. Five-year PFS and OS were 84.8±4.9% and 98.5±1.5% respectively. Five-year PFS of TP53 wild-type disease was 93.0±4.8%, compared with 51.7±13.6% in TP53 mutant (log-rank p0.001). Multivariate Cox regression analysis showed TP53 mutation was an independent risk factor for PFS (HR=10.175, 95%CI 2.615, 39.586, p 0.001), but not OS. Metastatic status, tumor resection extent, radiotherapy and chemotherapy sequence had no statistically significant impact on PFS and OS. Conclusion WNT-MB generally has good prognosis. Patients with somatic TP53 mutation have a higher risk of recurrence, caution should be exercised when considering treatment reduction in our patient population based on subgroup alone.
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