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@ARTICLE{Mateos:299789,
author = {M. K. Mateos and P. Ajuyah and N. Fuentes-Bolanos and S.
El-Kamand and P. Barahona and A.-K. Altekoester and C. Mayoh
and H. Holliday and J. Liu and L. Cui and E. Pfaff$^*$ and
A. Mackay and A. C. Resnick and M. Pinese and L. M. S. Lau
and D.-A. Khuong-Quang and K. Dias and C. Goudie and A.
Salkeld and J. L. Rokita and D. T. W. Jones$^*$ and N.
Juretic and E. Hayden and S. M. Pfister$^*$ and C. M. Kramm
and M. Blattner-Johnson$^*$ and N. Jabado and M. Tsoli and
O. Vittorio and S. Mueller and Y. Guo and K. Tucker and S.
M. Waszak and S. Perreault and C. Jones and M. Wong-Erasmus
and M. J. Cowley and D. S. Ziegler},
title = {{G}ermline analysis of an international cohort of pediatric
diffuse midline glioma patients.},
journal = {Neuro-Oncology},
volume = {27},
number = {7},
issn = {1522-8517},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2025-00544},
pages = {1849-1863},
year = {2025},
note = {2025 Sep 8;27(7):1849-1863},
abstract = {Factors that drive the development of diffuse midline
gliomas (DMG) are unknown. Our study aimed to determine the
prevalence of pathogenic/likely pathogenic (P/LP) germline
variants in pediatric patients with DMG.We assembled an
international cohort of 252 pediatric patients with DMG,
including diffuse intrinsic pontine glioma (n=153), with
germline whole genome or whole exome sequencing.We
identified P/LP germline variants in cancer predisposition
genes in $7.5\%$ (19/252) of patients. Tumor profiles
differed, with absence of somatic drivers in the PI3K/mTOR
pathway in patients with germline P/LP variants versus those
without (P = 0.023). P/LP germline variants were recurrent
in homologous recombination (n=9; BRCA1, BRCA2, PALB2) and
Fanconi anemia genes (n=4). Somatic findings established
that the germline variants definitively contributed to
tumorigenesis in at least $1\%$ of cases. One patient with
recurrent DMG and pathogenic germline variants (BRCA2,
FANCE) showed near-complete radiological response to PARP
and immune checkpoint inhibition.Our study determined the
prevalence of pathogenic germline variants in pediatric DMG,
and suggests a role in tumorigenesis for a subset of
patients.},
keywords = {PARP inhibitor (Other) / diffuse midline glioma (Other) /
germline variants (Other) / homologous recombination (Other)
/ pediatric (Other)},
cin = {B360 / B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B360-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40072012},
doi = {10.1093/neuonc/noaf061},
url = {https://inrepo02.dkfz.de/record/299789},
}