Molecular array analyses of 51 pediatric tumors shows overlap between malignant intracranial ectomesenchymoma and MPNST but not medulloblastoma or atypical teratoid rhabdoid tumor

Gene microarray has been used to identify prognostic markers and genes of interest for therapeutic targets; a less common use is to show possible histogenetic relationships between rare tumor types and more common neoplasms. Intracranial malignant ectomesenchymoma (MEM) is a pediatric tumor postulated to arise from neural crest cells that contain divergent neuroectodermal and mesenchymal tissues, principally mature ganglion cells and rhabdomyosarcoma (RMS). We investigated a case of MEM by molecular, cytogenetic, and gene array analyses and compared results with our previously unpublished series of 51 pediatric tumors including conventional RMS, Ewing sarcoma (EWS), medulloblastoma (MED), atypical teratoid rhabdoid tumor (ATRT), and malignant peripheral nerve sheath tumor (MPNST); the latter is a sarcoma also with potential for divergent differentiation. Standard cytogenetic analyses and RT-PCR testing for the classic gene rearrangements seen in RMS [t(2;13)-PAX3/FKHR] and EWS ([t(11;22) & t(21;22)-EWS/FLI-1 & EWS/ERG), were used for characterization of the MEM, with gene expression microarray analyses on all tumor types. Gene rearrangement studies were negative in MEM. Gene expression microarray analyses showed tight clustering of the MEM with the MPNST (n = 2), but divergence from other pediatric tumors. MEM and MPNST both showed complex karyotypes, but without diagnostic translocations. Despite the presence of malignant skeletal muscle differentiation in the MEM, gene array testing showed no overlap with RMS, MED, or ATRT, but rather with MPNST. This suggests a common stem cell origin or embryonic gene recapitulation for these tumors and provides novel insights into their underlying biology.