Subgroup and subtype-specific outcomes in adult medulloblastoma

AbstractMedulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p <  0.0001). Five-year progression-free survival (PFS) for WNT, SHH, Group 3, and Group 4 tumours was 64.4 (48.0–86.5), 61.9% (51.6–74.2), 80.0% (95% CI 51.6–100.0), and 44.9% (95% CI 28.6–70.7), respectively (p = 0.06). None of the clinical variables (age, sex, metastatic status, extent of resection, chemotherapy, radiotherapy) were associated with subgroup-specific PFS. Survival among patients with SHH tumours was significantly worse for cases with chromosome 3p loss (HR 2.9, 95% CI 1.1–7.6;p = 0.02), chromosome 10q loss (HR 4.6, 95% CI 2.3–9.4;p <  0.0001), chromosome 17p loss (HR 2.3, 95% CI 1.1–4.8;p = 0.02), andPTCH1 mutations (...
Source: Acta Neuropathologica - Category: Neurology Source Type: research