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Molecular characterization of medulloblastomas with extensive nodularity (MBEN).

Authors :
Korshunov, Andrey
Sahm, Felix
Stichel, Damian
Schrimpf, Daniel
Ryzhova, Marina
Zheludkova, Olga
Golanov, Andrey
Lichter, Peter
Jones, David T. W.
von Deimling, Andreas
Pfister, Stefan M.
Kool, Marcel
Source :
Acta Neuropathologica; Aug2018, Vol. 136 Issue 2, p303-313, 11p
Publication 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00016322
Volume :
136
Issue :
2
Database :
Complementary Index
Journal :
Acta Neuropathologica
Publication Type :
Academic Journal
Accession number :
130935534
Full Text :
https://doi.org/10.1007/s00401-018-1840-0