Multiple genomic alterations including N-myc amplification in a primary large cell medulloblastoma

The large cell (LC) subtype is a recently described histologic variant of medulloblastoma (Mb) associated with a rapid and aggressive clinical course. We describe the genomic profile of a LC-Mb tumor obtained from a patient who developed recurrent and fulminant disease despite 'good-risk' features at diagnosis and state- of-the-art multidisciplinary therapy. The tumor sample was analyzed using comparative genomic hybridization (CGH) and complementary molecular approaches. CGH revealed amplicons at chromosome bands 2p24-25, 2q12-22, and 17p11; losses of chromosomes 11q and 18; and low-level gains of 3q, 11p, 13q and 14q. Southern blot analysis confirmed N-myc amplification. No evidence of p53 mutation was detected. The genomic profile of this LC-Mb tumor sample revealed a distinctive pattern of genetic alterations including amplification of N-myc and anonymous oncogenes at chromosome bands 2q12-22 and 17p11. These genomic abnormalities are uncommon in other subtypes of Mb.