Abstract
In the last decade, around 24% of MYCN amplified (MNA) neuroblastomas (NB) at the CCRI contained a varying number of tumor cells/areas without MNA and were defined as heterogeneously MYCN amplified (hetMNA) according to INRG biology guidelines. For the investigation of the genomic background of hetMNA tumors, up to 4 pieces of the same tumor from 5 patients were analyzed by interphase FISH (I-FISH), MLPA and 250k SNP arrays. MNA was confirmed by at least one method. All tumors showed numeric chromosomal aberrations. Additionally, 3 patients displayed a variety of different segmental chromosomal aberrations (SCA) in at least one tumor piece. One patient showed two 1p-breakpoints in 4 pieces. MYCN/DDX1 I-FISH revealed different amplicon compositions in the same tumor piece of another patient. Investigation of genomic instability as initiator of MNA was done by γH2AX staining and revealed a pattern only partially correlating with MNA cells. Our data indicates the existence of multiple tumor cell clones in a single hetMNA NB. At the applied resolution, no common SCA is found to be underlying MNA.
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