Prognostic value of molecular, genetic and clinical characteristics of SHH group medulloblastoma

Abstract

SHH group of medulloblastoma is a heterogeneous tumor cohort. The neoplasms differ by biological characteristics as well as clinical features and prognosis of the disease. Purpose of the study is the analysis of clinical, molecular and genetic features for prognosis defining in patients with SHH group medulloblastoma. 28 patients with SHH group medulloblastomas were included in the study. The MB molecular group verification was performed in parallel by Nanostring gene expression profiling and immunohistochemical assessment of tumor samples. The detection of TP53 gene mutations was carried out with Sanger sequencing. The prognostic impact of the clinical, molecular and genetic factors of the disease was analyzed by calculating 5-years event-free survival (EFS). The median of follow up time achieved 38.9 months. All patients harboring the TP53 mutation (n = 3) had dismal outcome (two patients died from the progression of the disease, one patient has secondary tumor). Children from older age group ( > 3 years) had more adverse events comparing to younger children ( < 3 years): EFS 49.2 ± 31.3% vs. 78.8 ± 13.9%. The relapse of the disease occurred in 7 patients (25%). Notably, that in younger children the second line treatment was effective. The presence of TP53 mutations as well as age above 3 years are associated with poor prognosis in SHH group medulloblastomas. The novel molecular and genetics markers are needed for precise prognosis defining.