08 (2.98-3.18)) and MSAc cerebella (expression NVP-AUY922 ic50 change: 2.44 (2.14-2.88)). In the latter there was CysC overexpression in Pukinje

cells, Bergmann glia and dentate nucleus neurons. No cathepsin increase was detected in MSA cerebella. High mRNA levels of CST3 and cathepsins B and L1 were observed in SCA3 and CI brains. CysC changes are differentially present in the parkinsonian and cerebellar forms of MSA and may play an important role in the pathogenesis of this neurodegenerative condition. “
“Medulloblastoma is the most common paediatric malignant brain tumour. To identify altered genetic events in a comprehensive manner, we recently performed exome sequencing of a series of medulloblastomas [1]. This study identified mutations in genes involved in chromatin modification in 20% of patients examined, including the myeloid/lymphoid or mixed lineage leukaemia (MLL) family genes MLL2 and MLL3, which were not previously known to be associated with medulloblastoma [1]. The majority of those alterations were nonsense or frameshift mutations, indicating that MLL2 and MLL3 are new medulloblastoma tumour suppressor genes [1]. Subsequent exome sequencing studies further validated MLL2 pathway mutations as medulloblastoma

driver events [2-4]. In this report, we present detailed histopathological characteristics of three cases with MLL2/3 gene mutations. The male patient discussed in case 1 initially presented as a 5-year-old with a profound frontal headache associated with nausea and vomiting, following receipt of an immunization booster. Five days later the headache HA-1077 in vitro returned, and he was noted to have a gait imbalance; a magnetic resonance AG-014699 ic50 imaging scan showed a fourth ventricular mass (Figure 1A). Histopathological analysis revealed a medulloblastoma. Therapy consisted of craniospinal irradiation with a posterior fossa boost and chemotherapy consisting of a bone marrow transplant protocol

of vincristine, amifostine, cisplatin and cyclophosphamide. He is now 5 years post therapy without evidence of disease. Case 2 is of a male patient who presented as an 11-year-old who began to experience decreased appetite and headaches that awoke him, associated with nausea and vomiting. A computed tomography scan showed marked hydrocephalus with a 4-cm mass in the posterior fossa. Histopathological analysis identified a medulloblastoma. Post-operatively, he underwent craniospinal radiation therapy and chemotherapy with vincristine, cisplatin and cyclophosphamide supplemented with hyperalimentation via gastric tube placement. Now at 6 years post diagnosis, he is doing well at recent follow-up. Case 3 is a female patient who presented as a 7-year-old with a 3-week history of headache associated with morning nausea and vomiting, dizziness and recent onset of double vision. Radiographic studies revealed an enhancing mass lesion in the fourth ventricle. Axial and sagittal gadolinium-enhanced images demonstrated diffuse leptomeningeal spread of disease.