Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas.

Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.

Background: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.

Papillary Tumor of the Pineal Region: A Distinct Molecular Entity.

Papillary tumor of the pineal region (PTPR) is a neuroepithelial brain tumor, which might pose diagnostic difficulties and recurs often. Little is known about underlying molecular alterations. We therefore investigated chromosomal copy number alterations, DNA methylation patterns and mRNA expression profiles in a series of 24 PTPRs.

Pineal parenchymal tumours and pineal cysts.

Background And Purpose: Pineal parenchymal tumours (PPTs) and pineal cysts represent one third of the pineal region lesions. PPTs are subdivided into pineocytoma (PC), pineoblastoma (PB) and PPT with intermediate differentiation (PPTID). We report morphological and immunochemical features which permit to grade these tumours.

Anatomical, molecular and pathological consideration of the circumventricular organs.

Background And Purpose: Circumventricular organs (CVOs) are a diverse group of specialised structures characterized by peculiar vascular and position around the third and fourth ventricles of the brain. In humans, these organs are present during the fetal period and some become vestigial after birth. Some, such as the pineal gland (PG), subcommissural organ (SCO) and organum vasculosum of the lamina terminalis (OVLT), which are located around the third ventricle, might be the site of origin of periventricular tumours.

Histopathology of pineal germ cell tumors.

Germ cell tumors (GCTs) classically occur in gonads. However, they are the most frequent neoplasms in the pineal region. The pineal location of GCTs may be caused by the neoplastic transformation of a primordial germ cell that has mismigrated.

Papillary tumor of the pineal region: Histopathological characterization and review of the literature.

Background And Purpose: The papillary tumor of the pineal region (PTPR) was described as a distinct new entity for the first time in 2003 by our team and has been included in the last 2007 WHO classification of tumors of the Central Nervous System. We describe the histopathological characterization of PTPR and present a review of the literature.

Methods: The description of the histological and immunological features of PTPR is based on the 2007 WHO classification.

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma.

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner.

Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma.

Purpose: Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles.

Patients And Methods: We determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas.

Role of surgery, radiotherapy and chemotherapy in papillary tumors of the pineal region: a multicenter study.

Papillary tumor of the pineal region (PTPR), recently described as a distinct clinicopathological entity, can show aggressive biological behavior. The optimal therapeutic approach of PTPR has not been well defined. The role of surgery, radiotherapy, and chemotherapy in the treatment of PTPR was analyzed in a large multicenter series.

Complexity and developmental changes in the expression pattern of claudins at the blood-CSF barrier.

The choroid plexus epithelium controls the movement of solutes between the blood and the cerebrospinal fluid. It has been considered as a functionally more immature interface during brain development than in adult. The anatomical basis of this barrier is the interepithelial choroidal junction whose tightness has been attributed to the presence of claudins.

Subgroup-specific structural variation across 1,000 medulloblastoma genomes.

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas.

Molecular characterization of central neurocytomas: potential markers for tumor typing and progression.

Central neurocytomas (CNs) are rare intraventricular tumors presenting a favorable prognosis after surgery. Their transcriptomic profile is poorly characterized. We performed a microarray transcriptomic study to search for molecular markers that might improve diagnostic accuracy.

Histopathologic and ultrastructural features and claudin expression in papillary tumors of the pineal region: a multicenter analysis.

Neuroepithelial papillary tumor of the pineal region (PTPR) has been defined as a distinct entity that is increasingly being recognized, with 96 cases now reported. This tumor shares morphologic features with both ependymomas and choroid plexus tumors. PTPR is characterized by an epithelial-like growth pattern in which the vessels are covered by layers of tumor cells forming perivascular pseudorosettes.

Molecular characterization of circumventricular organs and third ventricle ependyma in the rat: potential markers for periventricular tumors.

Circumventricular organs (CVOs) are specialized ventricular structures around the third and fourth ventricles of the brain. In humans, these structures are present during the fetal period and some become vestigial after birth. Some of these organs, such as the pineal gland (PG), subcommissural organ (SCO), and organum vasculosum of the lamina terminalis, might be the sites of origin of periventricular tumors, notably pineal parenchymal tumors, papillary tumor of the pineal region and chordoid glioma.

Folate depletion changes gene expression of fatty acid metabolism, DNA synthesis, and circadian cycle in male mice.

Folate is essential for purine and thymidylate biosynthesis and in methyl transfer for DNA methylation. Folate deficiency alters the secretion of melatonin, a hormone involved in circadian rhythm entrainment, and causes hyperhomocysteinemia because of disruption of homocysteine metabolism. Adverse effects of homocysteine include the generation of free radicals, activation of proliferation or apoptosis, and alteration of gene expression.

Prognostic factors in central neurocytomas: a multicenter study of 71 cases.

Central neurocytoma (CN) is a rare intraventricular tumor presenting a benign histologic appearance and favorable prognosis after surgery. In contrast, "atypical" CN is defined by a high MIB1 proliferation index and/or histologic features of malignancy, which are associated with a poorer outcome. This variant of CN remains somewhat controversial.

Utility of Ki67 immunostaining in the grading of pineal parenchymal tumours: a multicentre study.

Aims: Pineal parenchymal tumours (PPTs) are rare neoplasms that are divided into pineocytoma (PC), pineoblastoma (PB) and PPT of intermediate differentiation (PPTID). Factors affecting the survival of patients with PPTs are morphological subtype and histological grading according to mitotic index and neurofilament immunostaining. Grading criteria to distinguish PPTIDs are difficult to define, particularly when using small specimens.

Cellular plasticity in the supraoptic and paraventricular nuclei after prolonged dehydration in the desert rodent Meriones shawi: Vasopressin and GFAP immunohistochemical study.

Supraoptic (SON) and paraventricular (PVN) nuclei are part of the hypothalamic-neurohypophysial system, they constitute the main source for vasopressin and they represent also obvious examples of activity-dependent neuroglial plasticity. Certain physiological conditions such as dehydration are accompanied by a structural remodeling of the neurons, their synaptic inputs and their surrounding glia. In the present work, an adult Meriones shawi (a rodent adapted to desert life) is used as an animal model.

Pleomorphic pineocytoma associated with normal pineal parenchyma: report of a case in a 70-year-old man.

Pineocytomas (PCs) most frequently occur in adults, but only three cases have been reported in women older than 70 years. In PCs, cytologic pleomorphism, accompanied by ganglion cells intensely expressing neuronal markers, has been described and the presence of pleomorphic cells may lead to an erroneous upgrading of the tumor. We report an unusual case of pleomorphic pineocytoma in an older patient who presented with a slowly growing tumor adjacent to residual pineal gland.

Histopathology of tumors of the pineal region.

Pineal region tumors are heterogeneous lesions and include mainly pineal parenchymal tumors (PPTs), papillary tumors of the pineal region (PTPRs) and germ cell tumors (GCTs). This article describes the cystic pineal gland compared with normal tissue and histopathological features of the most frequent pineal region tumors. PPTs are subdivided into pineocytoma (grade I), pineoblastoma (grade IV) and tumors with intermediate differentiation (PPTIDs; grades II-III).