TY  - JOUR
AU  - Korshunov, Andrey
AU  - Sahm, Felix
AU  - Stichel, Damian
AU  - Schrimpf, Daniel
AU  - Ryzhova, Marina
AU  - Zheludkova, Olga
AU  - Golanov, Andrey
AU  - Lichter, Peter
AU  - Jones, David
AU  - von Deimling, Andreas
AU  - Pfister, Stefan
AU  - Kool, Marcel
TI  - Molecular characterization of medulloblastomas with extensive nodularity (MBEN).
JO  - Acta neuropathologica
VL  - 136
IS  - 2
SN  - 1432-0533
CY  - Berlin
PB  - Springer
M1  - DKFZ-2018-01185
SP  - 303 - 313
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29569031
DO  - DOI:10.1007/s00401-018-1840-0
UR  - https://inrepo02.dkfz.de/record/136747
ER  -