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Therapeutic radiation for childhood cancer drives structural aberrations of NF2 in meningiomas

equally to this work. Kenneth D. Aldape and Gelareh Zadeh jointly supervised this work. AffiliationsMacFeeters Hamilton Centre for Neuro-Oncology Research, Princess Margaret Cancer Centre, University ... , Normand J. Laperriere, Kenneth D. Aldape & Gelareh ZadehDepartment of Surgery, Division of Neurosurgery, University of Toronto, Toronto, ON, Canada, M5S 1A8Suganth Suppiah, Michael D. Taylor & Gelareh

GBM's multifaceted landscape: highlighting regional and microenvironmental heterogeneity

Gliomas are a heterogeneous group of tumors that show variable proliferative potential, invasiveness, aggressiveness, histological grading, and clinical behavior. In this review, we focus on glioblastoma multiforme (GBM), a grade IV glioma, which is the most common and malignant of primary adult brain tumors. Research over the past several decades has revealed the existence of...

Discovering functional modules by identifying recurrent and mutually exclusive mutational patterns in tumors

D Aldape 4 Aleksandar Milosavljevic 0 0 Graduate Program in Structural and Computational Biology and Molecular Biophysics; and Department of Molecular and Human Genetics, Baylor College of Medicine

Bayesian ensemble methods for survival prediction in gene expression data

Motivation: We propose a Bayesian ensemble method for survival prediction in high-dimensional gene expression data. We specify a fully Bayesian hierarchical approach based on an ensemble ‘sum-of-trees’ model and illustrate our method using three popular survival models. Our non-parametric method incorporates both additive and interaction effects between genes, which results in...

A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity

Introduction There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. Methods We combined laser capture microdissection and gene expression...

The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants

Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2...

Molecular Subtypes of Glioblastoma Are Relevant to Lower Grade Glioma

Background Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM) expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas). Methods Gene expression array, single nucleotide polymorphism (SNP...

IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection

Background IDH1 gene mutations identify gliomas with a distinct molecular evolutionary origin. We sought to determine the impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomas—World Health Organization grade III anaplastic astrocytomas and grade IV glioblastoma.

A model of molecular interactions on short oligonucleotide microarrays

Cerveny Dana F Chace Ron L DeBlanc R Patrick Gearing Tim D Bovee Clay B Siegall Joseph A Francisco Alan F Wahl Damon L Meyer Peter D Senter Nat. Biotechnol. Li Zhang Michael F Miles Kenneth D Aldape Nat

Where are we now? And where are we going? A report from the Accelerate Brain Cancer Cure (ABC2) Low-grade Glioma Research Workshop

Jason T. Huse Max Wallace Kenneth D. Aldape Mitchel S. Berger Chetan Bettegowda Daniel J. Brat Daniel P. Cahill Timothy Cloughesy Daphne A. Haas-Kogan Marco Marra C. Ryan Miller Sarah J. Nelson Sofie

MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma

Hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene has been shown to be associated with improved outcome in glioblastoma (GBM) and may be a predictive marker of sensitivity to alkylating agents. However, the predictive utility of this marker has not been rigorously tested with regard to sensitivity to other therapies, namely radiation. To address this...

Randomized phase II adjuvant factorial study of dose-dense temozolomide alone and in combination with isotretinoin, celecoxib, and/or thalidomide for glioblastoma

Michael E. Salacz Justin D. Floyd Monica E. Loghin Sigmund H. Hsu Javier Gonzalez Eric L. Chang Shiao Y. Woo Anita Mahajan Kenneth D. Aldape W. K. Alfred Yung Mark R. Gilbert on behalf of the Anderson ... Y. Woo, Anita Mahajan, Kenneth D. Aldape: No conflicts to disclose. Morris D. Groves received research support from GSK and Merck, honoraria from Merck and Foundation Medicine. He is a consultant in

Next-generation sequencing-based multi-gene mutation profiling of solid tumors using fine needle aspiration samples: promises and challenges for routine clinical diagnostics

Increasing use of fine needle aspiration for oncological diagnosis, while minimally invasive, poses a challenge for molecular testing by traditional sequencing platforms due to high sample requirements. The advent of affordable benchtop next-generation sequencing platforms such as the semiconductor-based Ion Personal Genome Machine (PGM) Sequencer has facilitated multi-gene...

VEGF Trap induces antiglioma effect at different stages of disease

Pathological angiogenesis is a hallmark of cancer, specifically of glioblastomas, the most malignant and common primary brain tumor. Vascular endothelial growth factor (VEGF) is the key protein in the regulation of the hypervascular phenotype of primary malignant brain tumors. In this study, we tested VEGF Trap, a soluble decoy receptor for VEGF, in an intracranial glioma model...

Gamma-radiation sensitivity and polymorphisms in RAD51L1 modulate glioma risk

Background: DNA strand breaks pose the greatest threat to genomic stability. Genetically determined mutagen sensitivity predisposes individuals to a variety of cancers, including glioma. However, polymorphisms in DNA strand break repair genes that may determine mutagen sensitivity are not well studied in cancer risk, especially in gliomas. Methods: We correlated genotype data for...

Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays

Neubauer 4 Tamara J Nixon 4 Kenneth D Aldape 3 5 Gilbert J Cote 2 5 Ralf Krahe 1 4 5 0 Department of Bioinformatics and Computational Biology, University of Texas M. D. Anderson Cancer Center , Houston

Recursive partitioning analysis of prognostic variables in newly diagnosed anaplastic oligodendroglial tumors

Background Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision making or to combine them for prognostication.

Exploratory Analysis of the Copy Number Alterations in Glioblastoma Multiforme

Background The Cancer Genome Atlas project (TCGA) has initiated the analysis of multiple samples of a variety of tumor types, starting with glioblastoma multiforme. The analytical methods encompass genomic and transcriptomic information, as well as demographic and clinical data about the sample donors. The data create the opportunity for a systematic screening of the components...

Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma?

Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma...

Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma

Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic cells more precisely but may be inhibited by concurrent myelosuppressive chemotherapy like temozolomide (TMZ), which produces a...