The germline variants in DNA repair genes in pediatric medulloblastoma
Trubicka, Joanna ;  Zemojtel, Tomasz ;  Hecht, Jochen ;  Falana, Katarzyna ;  Piekutowska-Abramczuk, Dorota ;  Ploski, Rafal

Main titleThe germline variants in DNA repair genes in pediatric medulloblastoma
Subtitlea challenge for current therapeutic strategies
AuthorTrubicka, Joanna
AuthorZemojtel, Tomasz
AuthorHecht, Jochen
AuthorFalana, Katarzyna
AuthorPiekutowska-Abramczuk, Dorota
AuthorPloski, Rafal
No. of Pages11 S.
KeywordsMedulloblastoma; DNA repair genes; Toxicity
Classification (DDC)610 Medical sciences; Medicine
Also published inBMC Cancer. - 17 (2017), Artikel Nr. 239

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.


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.


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.


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.
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FU DepartmentDepartment of Medicine - Charité - University Medicine Berlin
Year of publication2017
Type of documentScience article
Terms of use/RightsCreative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors commentsDer Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
Created at2017-05-12 : 10:33:44
Last changed2017-05-12 : 10:45:41
Static URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000026987