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Background  The defects in DNA repair genes are potentially linked to development and response to therapy in  medulloblastoma . Therefore the purpose of this study was to establish the spectrum and frequency of germline variants in selected DNA repair genes and their impact on response to chemotherapy in  medulloblastoma  patients.    Methods  The following genes were investigated in 102 paediatric patients:  MSH2  and  RAD50  using targeted gene panel sequencing and  NBN  variants (p.I171V and p.K219fs*19) by Sanger sequencing. In three patients with presence of rare life-threatening adverse events (AE) and no detected variants in the analyzed genes, whole exome sequencing was performed. Based on combination of molecular and immunohistochemical evaluations tumors were divided into molecular subgroups. Presence of variants was tested for potential association with the occurrence of rare life-threatening AE and other clinical features.    Results  We have identified altogether six new potentially pathogenic variants in  MSH2  (p.A733T and p.V606I),  RAD50  (p.R1093*),  FANCM  (p.L694*),  ERCC2  (p.R695C) and  EXO1  (p.V738L), in addition to two known  NBN  variants. Five out of twelve patients with defects in either of  MSH2 ,  RAD50  and  NBN  genes suffered from rare life-threatening AE, more frequently than in control group ( p  = 0.0005). When all detected variants were taken into account, the majority of patients (8 out of 15) suffered from life-threatening toxicity during chemotherapy.    Conclusion  Our results, based on the largest systematic study performed in a clinical setting, provide preliminary evidence for a link between defects in DNA repair genes and treatment related toxicity in children with  medulloblastoma . The data suggest that patients with DNA repair gene variants could need special vigilance during and after courses of chemotherapy.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-017-3211-y) contains supplementary material, which is available to authorized users.

The germline variants in DNA repair genes in pediatric medulloblastoma: a challenge for current therapeutic strategies