PAK3 is a key signature gene of the glioma proneural subtype and affects its proliferation, differentiation and growth.

Purpose: Gliomas are the most lethal adult primary brain cancers. Recent advances in their molecular characterization have contributed to a better understanding of their pathophysiology, but there is still a need to identify key genes controling glioma cell proliferation and differentiation. The p21-activated kinases PAK1 and PAK2 play essential roles in cell division and brain development and are well-known oncogenes.

A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas.

Chordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA mutation.

TCF12 is mutated in anaplastic oligodendroglioma.

Anaplastic oligodendroglioma (AO) are rare primary brain tumours that are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosomes 1p/19q co-deletion and an IDH mutation. Here we analysed 51 AO by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1.

CIC inactivating mutations identify aggressive subset of 1p19q codeleted gliomas.

Objective: CIC gene is frequently mutated in oligodendroglial tumors with 1p19q codeletion. However, clinical and biological impact remain poorly understood.

Methods: We sequenced the CIC gene on 127 oligodendroglial tumors (109 with the 1p19q codeletion) and analyzed patients' outcome.

TERT promoter mutations in gliomas, genetic associations and clinico-pathological correlations.

Background: The role of telomerase reverse transcriptase (TERT) in gliomagenesis has been recently further strengthened by the frequent occurrence of TERT promoter mutations (TERTp-mut) in gliomas and evidence that the TERT SNP genetic rs2736100 influences glioma risk. TERTp-mut creates a binding site for Ets/TCF transcription factors, whereas the common rs2853669 polymorphism disrupts another Ets/TCF site on TERT promoter.

Methods: We sequenced for TERTp-mut in 807 glioma DNAs and in 235 blood DNAs and analysed TERT expression by RT-PCR in 151 samples.

IDH mutations: genotype-phenotype correlation and prognostic impact.

IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1(R132H) , IDH1(nonR132H) , and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1(nonR132H) in astrocytic tumors.

The V-ATPase membrane domain is a sensor of granular pH that controls the exocytotic machinery.

Several studies have suggested that the V0 domain of the vacuolar-type H(+)-adenosine triphosphatase (V-ATPase) is directly implicated in secretory vesicle exocytosis through a role in membrane fusion. We report in this paper that there was a rapid decrease in neurotransmitter release after acute photoinactivation of the V0 a1-I subunit in neuronal pairs. Likewise, inactivation of the V0 a1-I subunit in chromaffin cells resulted in a decreased frequency and prolonged kinetics of amperometric spikes induced by depolarization, with shortening of the fusion pore open time.

KIAA1549-BRAF fusions and IDH mutations can coexist in diffuse gliomas of adults.

KIAA1549-BRAF fusion gene and isocitrate dehydrogenase (IDH) mutations are considered two mutually exclusive genetic events in pilocytic astrocytomas and diffuse gliomas, respectively. We investigated the presence of the KIAA1549-BRAF fusion gene in conjunction with IDH mutations and 1p/19q loss in 185 adult diffuse gliomas. Moreover BRAF(v600E) mutation was also screened.

The renal v-ATPase a4 subunit is expressed in specific subtypes of human gliomas.

Vacuolar H(+) -ATPases (v-ATPases) are multimeric proton pumps which acidify various intra-cellular organelles and may participate in pHe and pHi regulation in cancer cell lines. The ATP6V0A4 gene encodes the a4 subunit which is expressed in kidney and epididymis. Because we found a4 mRNA highly expressed in C6Bu1 glioma cell line, we measured it in 205 glioma biopsies and 11 brain biopsies from epileptic patients.

Impact of walking epidural analgesia on obstetric outcome of nulliparous women in spontaneous labour.

Background: To explore the effects of walking epidural analgesia on obstetric and neonatal outcomes, we performed a case-control study.

Method: Each nulliparous woman receiving walking epidural analgesia using 0.0625% bupivacaine (n = 44) was matched to two nulliparous historical controls receiving 0.