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@ARTICLE{Pfaff:147769,
author = {E. Pfaff$^*$ and C. Aichmüller$^*$ and M. Sill$^*$ and D.
Stichel$^*$ and M. Snuderl and M. A. Karajannis and M. U.
Schuhmann and J. Schittenhelm and M. Hasselblatt and C.
Thomas and A. Korshunov$^*$ and M. Rhizova and A.
Wittmann$^*$ and A. Kaufhold$^*$ and M. Iskar$^*$ and P.
Ketteler and D. Lohmann and B. A. Orr and D. W. Ellison and
K. von Hoff and M. Mynarek and S. Rutkowski and F. Sahm$^*$
and A. von Deimling$^*$ and P. Lichter$^*$ and M. Kool$^*$
and M. Zapatka$^*$ and S. M. Pfister$^*$ and D. Jones$^*$},
title = {{M}olecular subgrouping of primary pineal parenchymal
tumors reveals distinct subtypes correlated with clinical
parameters and genetic alterations.},
journal = {Acta neuropathologica},
volume = {139},
number = {2},
issn = {1432-0533},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2019-02743},
pages = {243-257},
year = {2020},
note = {#EA:B360#LA:B360#2020 Feb;139(2):243-257.},
abstract = {Tumors of the pineal region comprise several different
entities with distinct clinical and histopathological
features. Whereas some entities predominantly affect adults,
pineoblastoma (PB) constitutes a highly aggressive
malignancy of childhood with a poor outcome. PBs mainly
arise sporadically, but may also occur in the context of
cancer predisposition syndromes including DICER1 and RB1
germline mutation. With this study, we investigate
clinico-pathological subgroups of pineal tumors and further
characterize their biological features. We performed
genome-wide DNA methylation analysis in 195 tumors of the
pineal region and 20 normal pineal gland controls.
Copy-number profiles were obtained from DNA methylation
data; gene panel sequencing was added for 93 tumors and
analysis was further complemented by miRNA sequencing for 22
tumor samples. Unsupervised clustering based on DNA
methylation profiling separated known subgroups, like
pineocytoma, pineal parenchymal tumor of intermediate
differentiation, papillary tumor of the pineal region and
PB, and further distinct subtypes within these groups,
including three subtypes within the core PB subgroup. The
novel molecular subgroup Pin-RB includes cases of trilateral
retinoblastoma as well as sporadic pineal tumors with RB1
alterations, and displays similarities with retinoblastoma.
Distinct clinical associations discriminate the second novel
molecular subgroup PB-MYC from other PB cases. Alterations
within the miRNA processing pathway (affecting DROSHA, DGCR8
or DICER1) are found in about two thirds of cases in the
three core PB subtypes. Methylation profiling revealed
biologically distinct groups of pineal tumors with specific
clinical and molecular features. Our findings provide a
foundation for further clinical as well as molecular and
functional characterization of PB and other pineal tumors,
including the role of miRNA processing defects in
oncogenesis.},
cin = {B360 / B060 / B062 / B300 / HD01},
ddc = {610},
cid = {I:(DE-He78)B360-20160331 / I:(DE-He78)B060-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)B300-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31768671},
doi = {10.1007/s00401-019-02101-0},
url = {https://inrepo02.dkfz.de/record/147769},
}