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@ARTICLE{Korshunov:136747,
author = {A. Korshunov$^*$ and F. Sahm$^*$ and D. Stichel$^*$ and D.
Schrimpf$^*$ and M. Ryzhova and O. Zheludkova and A. Golanov
and P. Lichter$^*$ and D. Jones$^*$ and A. von Deimling$^*$
and S. Pfister$^*$ and M. Kool$^*$},
title = {{M}olecular characterization of medulloblastomas with
extensive nodularity ({MBEN}).},
journal = {Acta neuropathologica},
volume = {136},
number = {2},
issn = {1432-0533},
address = {Berlin},
publisher = {Springer},
reportid = {DKFZ-2018-01185},
pages = {303 - 313},
year = {2018},
abstract = {Medulloblastoma with extensive nodularity (MBEN) is a rare
histological variant of medulloblastoma (MB). These tumors
are usually occurring in the first 3 years of life and are
associated with good prognosis. Molecular analyses of MBEN,
mostly limited to single cases or small series, have shown
that they always classify as sonic hedgehog (SHH)-driven MB.
Here, we have analyzed 25 MBEN through genome-wide DNA
methylation, copy-number profiling and targeted
next-generation sequencing. Results of these analyses were
compared with molecular profiles of other SHH MB
histological variants. As expected, the vast majority of
MBEN (23/25) disclosed SHH-associated epigenetic signatures
and mutational landscapes but, surprisingly, two MBEN were
classified as Group 3/4 MB. Most MBEN classified as SHH MB
displayed SHH-related and mutually exclusive mutations in
either SUFU, or PTCH1, or SMO at similar frequencies.
However, only SUFU mutations were also identified in the
germ-line. Most of SUFU-associated MBEN eventually recurred
but patients were treated successfully with second-line
high-dose chemotherapy. Altogether, our data show that risk
stratification even for well-recognizable histologies such
as MBEN cannot rely on histology alone but should include
additional molecular analyses such as methylation profiling
and DNA sequencing. For all patients with 'MBEN' histology,
we recommend sequencing SUFU and PTCH1 in the tumor as well
as in the germ-line for further clinical stratification and
choice of the optimal treatment strategy upfront.},
cin = {G380 / L101 / B060 / B062},
ddc = {610},
cid = {I:(DE-He78)G380-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)B060-20160331 / I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29569031},
doi = {10.1007/s00401-018-1840-0},
url = {https://inrepo02.dkfz.de/record/136747},
}