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

HaupttitelThe germline variants in DNA repair genes in pediatric medulloblastoma
Titelzusatza challenge for current therapeutic strategies
AutorTrubicka, Joanna
AutorZemojtel, Tomasz
AutorHecht, Jochen
AutorFalana, Katarzyna
AutorPiekutowska-Abramczuk, Dorota
AutorPloski, Rafal
Seitenzahl11 S.
Freie SchlagwörterMedulloblastoma; DNA repair genes; Toxicity
DDC610 Medizin und Gesundheit
Auch erschienen inBMC Cancer. - 17 (2017), Artikel Nr. 239
ZusammenfassungBackground

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.
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Fachbereich/EinrichtungMedizinische Fakultät Charité - Universitätsmedizin Berlin
Erscheinungsjahr2017
Dokumententyp/-SammlungenWissenschaftlicher Artikel
SpracheEnglisch
RechteCreative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Anmerkungen des AutorsDer Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
Erstellt am12.05.2017 - 10:33:44
Letzte Änderung12.05.2017 - 10:45:41
 
Statische URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000026987
DOI10.1186/s12885-017-3211-y
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