A Novel Pseudogene Methylation Signature to Predict Temozolomide Outcome in Non-G-CIMP Glioblastomas.

Objective: Alterations in the methylation state of pseudogenes may serve as clinically useful biomarkers of glioblastomas (GBMs) that do not have glioma-CpG island methylator phenotype (G-CIMP).

Methods: Non-G-CIMP GBM datasets were included for evaluation, and a RISK-score signature was determined from the methylation state of pseudogene loci. Both bioinformatic and experimental analyses were performed for biological validation.

Aberrant DNA methylation impacts HOX genes expression in bone marrow mesenchymal stromal cells of myelodysplastic syndromes and de novo acute myeloid leukemia.

DNA methylation, a major biological process regulating the transcription, contributes to the pathophysiology of hematologic malignancies, and hypomethylating agents are commonly used to treat myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML). In these diseases, bone marrow mesenchymal stromal cells (MSCs) play a key supportive role through the production of various signals and interactions. The DNA methylation status of MSCs, likely to reflect their functionality, might be relevant to understand their contribution to the pathophysiology of these diseases.

Integrative analysis identifies an immune-relevant epigenetic signature for prognostication of non-G-CIMP glioblastomas.

The clinical and molecular implications of DNA methylation alterations remain unclear among the majority of glioblastomas (GBMs) without glioma-CpGs island methylator phenotype (G-CIMP); integrative multi-level molecular profiling may provide useful information. Independent cohorts of non-G-CIMP GBMs or wild type (wt) lower-grade gliomas (LGGs) from local and public databases with DNA methylation and gene expression microarray data were included for discovery and validation of a multimarker signature, combined using a RISK score model. Bioinformatic and functional analyses were employed for biological validation.

EZH2 and KDM6B Expressions Are Associated with Specific Epigenetic Signatures during EMT in Non Small Cell Lung Carcinomas.

The role of Epigenetics in Epithelial Mesenchymal Transition (EMT) has recently emerged. Two epigenetic enzymes with paradoxical roles have previously been associated to EMT, EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 (PRC2) Subunit), a lysine methyltranserase able to add the H3K27me3 mark, and the histone demethylase KDM6B (Lysine Demethylase 6B), which can remove the H3K27me3 mark. Nevertheless, it still remains unclear how these enzymes, with apparent opposite activities, could both promote EMT.

Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation/chemotherapy in vivo.

Glioblastoma multiforme (GBM) is the most severe primary brain cancer. Despite an aggressive treatment comprising surgical resection and radio/chemotherapy, patient's survival post diagnosis remains short. A limitation for success in finding novel improved therapeutic options for such dismal disease partly lies in the lack of a relevant animal model that accurately recapitulates patient disease and standard of care.

Implementation of a molecular tumor board at a regional level to improve access to targeted therapy.

Background: With the development of precision oncology, Molecular Tumor Boards (MTB) are developing in many institutions. However, the implementation of MTB in routine clinical practice has still not been thoroughly studied.

Material And Methods: Since the first drugs approved for targeted therapies, patient tumor samples were centralized to genomic testing platforms.

Cytosine methylation of mature microRNAs inhibits their functions and is associated with poor prognosis in glioblastoma multiforme.

Background: Literature reports that mature microRNA (miRNA) can be methylated at adenosine, guanosine and cytosine. However, the molecular mechanisms involved in cytosine methylation of miRNAs have not yet been fully elucidated. Here we investigated the biological role and underlying mechanism of cytosine methylation in miRNAs in glioblastoma multiforme (GBM).

Clinical outcomes of non-small-cell lung cancer patients with BRAF mutations: results from the French Cooperative Thoracic Intergroup biomarkers France study.

Introduction: Patients with stage IV non-small-cell lung cancer (NSCLC) and BRAF V600 mutations may benefit from targeted therapies. Chemotherapy outcomes are little known in this population.

Methods: The French Cooperative Thoracic Intergroup (IFCT) Biomarkers France study was a national prospective cohort study aiming to describe the molecular characteristics and clinical outcome of all consecutive NSCLC patients (N = 17,664) screened for molecular alterations.

Novel predictive epigenetic signature for temozolomide in non-G-CIMP glioblastomas.

Objective: To identify novel epigenetic signatures that could provide predictive information that is complementary to promoter methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) gene for predicting temozolomide (TMZ) response, among glioblastomas (GBMs) without glioma-CpGs island methylator phenotype (G-CIMP) METHODS: Different cohorts of primary non-G-CIMP GBMs with genome-wide DNA methylation microarray data were included for discovery and validation of a multimarker signature, combined using a RISK score model. Different statistical analyses and functional experiments were performed for clinical and biological validation.

Results: By employing discovery cohorts with radiotherapy (RT) and TMZ versus RT alone and a strict multistep selection strategy, we identified seven CpGs, each of which was significantly correlated with overall survival (OS) of non-G-CIMP GBMs with RT/TMZ, independent of age, MGMT promoter methylation status, and other identified CpGs.

A five-CpG signature of microRNA methylation in non-G-CIMP glioblastoma.

Aims: DNA methylation has been found to regulate microRNAs (miRNAs) expression, but the prognostic value of miRNA-related DNA methylation aberration remained largely elusive in cancers including glioblastomas (GBMs). This study aimed to investigate the clinical and biological feature of miRNA methylation in GBMs of non-glioma-CpG island methylator phenotype (non-G-CIMP).

Methods: Prognostic miRNA methylation loci were analyzed, with TCGA and Rennes cohort as training sets, and independent datasets of GBMs and low-grade gliomas (LGGs) were obtained as validation sets.

Correction to: Neuro-radiological characteristics of adult diffuse grade II and III insular gliomas classified according to WHO 2016.

In the initial, online publication, the authors' given names were captured as family names and vice versa. The names are correctly shown here. The original article has been corrected.

Metastatic Clear-cell Renal Cell Carcinoma With a Long-term Response to Sunitinib: A Distinct Phenotype Independently Associated With Low PD-L1 Expression.

Background: Long-term responders (LTRs) are defined by at least 18 months of response to sunitinib in metastatic clear-cell renal cell carcinoma (ccRCC). Well-described by clinical studies, the phenotype of these tumors has never been explored.

Patients And Methods: In a retrospective and multicenter study, 90 ccRCCs of patients with metastatic disease were analyzed.

EMT is associated with an epigenetic signature of ECM remodeling genes.

Type III epithelial-mesenchymal transition (EMT) has been previously associated with increased cell migration, invasion, metastasis, and therefore cancer aggressiveness. This reversible process is associated with an important gene expression reprogramming mainly due to epigenetic plasticity. Nevertheless, most of the studies describing the central role of epigenetic modifications during EMT were performed in a single-cell model and using only one mode of EMT induction.

Neuro-radiological characteristics of adult diffuse grade II and III insular gliomas classified according to WHO 2016.

Introduction: The phenotypic heterogeneity of diffuse gliomas is still inconsistently explained by known molecular abnormalities. Here, we report the molecular and radiological features of diffuse grade WHO II and III gliomas involving the insula and its potential impact on prognosis.

Methods: Clinical, pathological, molecular and neuro-radiological features of 43 consecutive patients who underwent a surgical resection between 2006 and 2013 for a grade II and III gliomas involving the insula was retrospectively analyzed.

[Not Available].

PREDICTIVE BIOMARKERS OF RESPONSE TO IMMUNE CHECKPOINT INHIBITORS: PD-1 checkpoint inhibitors are becoming the reference treatment for several types of cancers. Many patients show remarkable efficacy and low toxicity. However, some patients have a better outcome than others with PD-1 checkpoint inhibitors.

The expression of EMX2 lead to cell cycle arrest in glioblastoma cell line.

Background: Glioblastoma (GB) is a highly invasive primary brain tumor that nearly always systematically recurs at the site of resection despite aggressive radio-chemotherapy. Previously, we reported a gene expression signature related to tumor infiltration. Within this signature, the EMX2 gene encodes a homeodomain transcription factor that we found was down regulated in glioblastoma.

Integration of transcriptome and proteome profiles in glioblastoma: looking for the missing link.

Background: Glioblastoma (GB) is the most common and aggressive tumor of the brain. Genotype-based approaches and independent analyses of the transcriptome or the proteome have led to progress in understanding the underlying biology of GB. Joint transcriptome and proteome profiling may reveal new biological insights, and identify pathogenic mechanisms or therapeutic targets for GB therapy.

A novel prognostic six-CpG signature in glioblastomas.

Aims: We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM).

Methods: A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation.

Dual IRE1 RNase functions dictate glioblastoma development.

Proteostasis imbalance is emerging as a major hallmark of cancer, driving tumor aggressiveness. Evidence suggests that the endoplasmic reticulum (ER), a major site for protein folding and quality control, plays a critical role in cancer development. This concept is valid in glioblastoma multiform (GBM), the most lethal primary brain cancer with no effective treatment.