Molecular profiling of a rare rosette-forming glioneuronal tumor arising in the spinal cord

Rosette-forming glioneuronal tumor (RGNT) of the IV ventricle is a rare and recently recognized brain tumor entity. It is histologically composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a component forming neurocytic rosettes and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in the spinal cord. Following an immunohistochemistry validation, we further performed an extensive genomic analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. We observed the loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Local amplifications in 9q34.2 and 19p13.3 (encompassing the gene SBNO2) were identified. Moreover, we observed focal gains/losses in several chromosomes. Additionally, on chromosome 7, we identified the presence of the KIAA1549:BRAF gene fusion, which was further validated by RT-PCR and FISH. Across all mutational analyses, we detected and validated the somatic mutations of the genes MLL2, CNNM3, PCDHGC4 and SCN1A. Our comprehensive molecular profiling of this RGNT suggests that MAPK pathway and methylome changes, driven by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity.Conselho Nacional de Desenvolvimento Científico e Tecnológico [475358/2011-2] to RMR (www.cnpq.br); Fundação de Amparo a Pesquisa do Estado de São Paulo [2012/19590-0] to RMR and [2011/08523-7 and 2012/08287-4] to LTB (www.fapesp.br); the Foundation for Science and Technology (FCT) [PTDC/SAU-ONC/115513/2009] to RMR; and the National Cancer Institute [P30CA046934] to MG

Neural encoding of food and monetary reward delivery

Different types of rewards such as food and money can similarly drive our behavior owing to shared brain processes encoding their subjective value. However, while the value of money is abstract and needs to be learned, the value of food is rooted in the innate processing of sensory properties and nutritional utilization. Yet, the actual consumption of food and the receipt of money have never been directly contrasted in the same experiment, questioning what unique neural processes differentiate those reward types. To fill this gap, we examined the distinct and common neural responses to the delivery of food and monetary rewards during fMRI.In a novel experimental approach, we parametrically manipulated the subjective value of food and monetary rewards by modulating the quantities of administered palatable milkshake and monetary gains. The receipt of increasing amounts of milkshake and money recruited the ventral striatum and the ventromedial prefrontal cortex, previously associated with value encoding. Notably, the consumption and the subsequent evaluation of increasing quantities of milkshake relative to money revealed an extended recruitment of brain regions related to taste, somatosensory processing, and salience. Moreover, we detected a decline of reward encoding in the ventral tegmental area, nucleus accumbens, and vmPFC, indicating that these regions may be susceptible to time-dependent effects upon accumulation of food and money rewards.Relative to monetary gains, the consumption and evaluation of palatable milkshakes engaged complex neural processing over and above value tracking, emphasizing the critical contribution of taste and other sensory properties to the processing of food rewards. Furthermore, our results highlight the need to closely monitor metabolic states and neural responses to the accumulation of rewards to pinpoint the mechanisms underlying time-dependent dynamics of reward-related processing