ID #345 Clinicopathological and molecular correlation of TERT-promoter mutations in medulloblastoma.

Background TERT promoter(TERTp) mutation has become an emerging marker of the adult subtype of SHH-activated medulloblastoma(MB), which is associated with a better prognosis. The study aims to evaluate correlation of TERTp mutations with various clinical, histoarchitectural and molecular features in MB. Materials and Methods Histologically and molecularly diagnosed cases of MB by targeted gene expression profiling(GEP) between the years 2021-2024 were evaluated for TERTp mutation by Droplet digital PCR(DdPCR) Results In a cohort of 201 cases, age range were-0-3years: 32(15.9%), 4-6years: 47(23.4%), 7-18years: 85(42.3%), 19-25years: 17(8.4%), 26-39 years: 18(8.9%) and ≥40years: 2(1%).M:F ratio-2.0:1. The cases were molecularly grouped as WNT-activated(n = 35,17.4%), SHH-activated and TP53 wildtype immunophenotype(64,31.8%), SHH-activated and TP53 mutant immunophenotype(3,1.4%) and non-WNT/non-SHH group[99(49.2%)- 32(15.9%)group3, 55(27.3%)group4, 12(5.9%)unclassified]. Classic(n = 138,68.6%) histoarchitecture was the most common followed by D/N (n = 38,18.9%) ,LC/A(n = 15,7.5%), with myogenic differentiation(NOS; n = 6,2.9%) and MBEN(n = 4,2%) histoarchitecture.Overall frequency of TERTp mutation was 16.9% (n = 34). 29 were of C228T and 5 were of C250T type of mutations. TERTp mutations were significantly associated with adult age-group (≥19 years) and SHH-activated group(p < 0.001). The frequency of mutation was 6.1% (n = 10) and 70.3% (n = 29) in ≤ 18 years and >18 years respectively. Among mutant cases,30-SHH-activated cases, 2 non-WNT/non-SHH group, and 2 WNT-activated cases (p < 0.001). 14(8.6%) were midline and 20(54.1%) were laterally localized tumours.17 cases showed classic and 17 showed D/N histoarchitecture. None of the mutant cases showed TP53-mutant immunophenotype, monosomy 6, and MYCN amplification. The one-year OS for TERTp mutant cases was better than TERT promoter wild-type cases. Conclusion TERTp mutations were common(92.3%) in adult SHH-activated MB patients, observed across classic and D/N histoarchitectural patterns, predominantly in lateralized locations, absent in MYCN-amplified and TP53-mutated cases, and associated with better overall survival.