Molecular characterization of medulloblastomas with extensive nodularity (MBEN)

AbstractMedulloblastoma 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 ta rgeted 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 classifie d as Group 3/4 MB. Most MBEN classified as SHH MB displayed SHH-related and mutually exclusive mutations in eitherSUFU, orPTCH1, orSMO at similar frequencies. However, onlySUFU mutations were also identified in the germ-line. Most ofSUFU-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 sequencingSUFU andPTCH1 in the tumor as well as in the germ-line for further clinical stra...
Source: Acta Neuropathologica - Category: Neurology Source Type: research