dc.contributor.author
Trubicka, Joanna
dc.contributor.author
Zemojtel, Tomasz
dc.contributor.author
Hecht, Jochen
dc.contributor.author
Falana, Katarzyna
dc.contributor.author
Piekutowska-Abramczuk, Dorota
dc.contributor.author
Ploski, Rafal
dc.date.accessioned
2018-06-08T11:11:13Z
dc.date.available
2017-05-12T10:45:41.608Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/21775
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-25063
dc.description.abstract
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.
de
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Medulloblastoma
dc.subject
DNA repair genes
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
The germline variants in DNA repair genes in pediatric medulloblastoma
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
BMC Cancer. - 17 (2017), Artikel Nr. 239
dc.title.subtitle
a challenge for current therapeutic strategies
dcterms.bibliographicCitation.doi
10.1186/s12885-017-3211-y
dcterms.bibliographicCitation.url
http://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3211-y
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000026987
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008167
dcterms.accessRights.openaire
open access