Embryonal Tumors with Abundant Neuropil and True Rosettes (ETANTR) is a rare variant of a CNS tumor in children and to date less than 75 cases have been reported. The prognosis is dismal and the rarity of this tumor has precluded defining oncogenic signaling pathways and treatment guidelines. We describe a 5 year female who presented at 3 years of age with ptosis of the left eye. MRI showed a large left frontoparietal mass with extension into the ethmoidal and maxillary sinuses. A partial resection of the mass was performed and the pathology was consistent with ETANTR. She received chemotherapy with vincristine, methotrexate, cytoxan, cisplatin, topotecan. As tumor continued to progress she received radiation therapy and adjuvant chemotherapy with temozolomide, etoposide followed by cis-retinoic acid and melatonin for a year. We for the first time, performed molecular tumor profiling using morphoproteomic analysis by quantifying immunohistochemical signaling intensity of major pathways and biological markers in this biomorphic tumor which included medulloepitheliomatous (ME) and the neuroblastic (NB) component. Analysis of the upstream signal transducers, downstream effectors, cell cycle related analytes, antiapoptotic and stem cell markers were performed. We demonstrated constitutive activation of the ras/Raf kinase/ERK pathway as evidenced by the phosphoyrylated ERK 1,2 kinase more seen in the ME portion and the Akt /mTOR pathway both in the nuclear and cytoplasmic compartments of the tumor cells. Constitutive activation of the NF-kappaB pathway was also seen which is consistent with the convergent signaling from the AKT and ERK pathways which showed the likely role of these major pathways in the oncogenesis of this tumor. This preliminary data shows targeting these combined pathways along with careful selection of conventional therapy could improve the prognosis of these rare aggressive tumors and warrants further evaluation in future studies. As persons with Down syndrome (DS) have a unique tumor profile with a reduced frequency of solid tumors, we aimed at evaluating the distribution and frequency of specific types of brain tumors. Medulloblastomas, Central Nervous System Primitive Neuroectodermal Tumors (CNS-PNETs) and gliomas were collected from cancer registries or brain tumor registries in 13 countries of Europe, America, Asia and Oceania. The observed number of children with DS having medulloblastomas, CNS-PNETs or glial tumors was compared to the expected number. The number of DS children with each category of tumor, medulloblastomas, CNS-PNETs and gliomas was treated as a Poisson variable with 0.000884 times the number of tumor cases in that category. Among 8,043 neural tumors: 6,882 medulloblastomas and 1,161 CNS-PNETs, only one patient with DS had a medulloblastoma, while respectively 6.08 (p ¼ 0.016) and 7.11 (p ¼ 0.0066) children with DS were expected. Among 13,797 children with gliomas, 10 had DS, whereas 12.2 were expected. Children with DS seem specifically protected against primary neural cel...
