The Peter Pan Syndrome: Oncohistones Stall Development in Pediatric Cancers

CCR Grand Rounds Dr. Jabado ’ s research focuses on elucidating genetic signatures of pediatric astrocytomas and examining how they compare to adults. These are deadly brain tumors that originate in the brain and include glioblastomas (GBM, the highest grade of astrocytomas), which are one of the deadliest cancers in humans. Her group uncovered that pediatric high-grade astrocytomas (HGA) are molecularly and genetically distinct from adult tumors. They also identified a new molecular mechanism driving pediatric HGA, namely recurrent somatic driver mutations in the tail of histone 3 variants (H3.3 and H3.1). These mutations lead to amino acid substitutions at key residues and are tightly correlated with a distinct global DNA methylation pattern, neuroanatomical locations and age specificities. Dr. Jabado ’ s and her team ’ s research findings position them as leaders in the field of HGA, and at the forefront of significant breakthroughs for this deadly brain tumor. Ultimately, based on these findings, patients could be stratified based on their genetic/molecular signature, and assigned to a beneficial therapeutic strategy, bringing needed effective interventions in this devastating cancer. Additionally, Dr. Jabado and her colleagues established a TCGA-like initiative by creating the International CHildhood Astrocytoma INtegrated Genomic and Epigenomic (ICHANGE) Consortium. This is a unique set of resources which enables the scientific world to investigate ast...
Source: Videocast - All Events - Category: General Medicine Tags: Upcoming Events Source Type: video

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Abstract Over twenty thousand persons rely on water from Atuwara River for drinking and other domestic purposes, hence the need to ascertain the human health risk inherent in such practice. Seventy-two water samples were collected from River Atuwara during the dry and wet seasons of 2018, and the concentration of heavy metals (Pb, As, Ni, Cr, Zn, Cu, and Cd) were measured using ICP-OES. A newly developed human health risk assessment method, HHRISK code was used to estimate the health risks associated with consumption of water from Atuwara River. Results obtained revealed that the concentration of heavy metals in t...
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
Abstract There is limited information about pesticide contamination in Iran's agricultural land, particularly in plains producing exportable fruits. The aim of this investigation was to evaluate the concentration of organochlorine pesticides (OCPs) including hexachlorocyclohexane (HCH), heptachlor, dichloro-diphenyl-trichloroethane (DDT), chlordane (CHL), and their isomers compounds in agricultural soils of southern Iran. A total of 28 topsoil samples were collected from agricultural lands of Dalaki and Shabankare areas, Bushehr, Iran. In Dalaki area, the mean value of ΣHCH (α, β, γ, δ...
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
Conclusion: ARL is a heterogeneous disease. Histologic subtype is a major determinant of the clinical outcome. ADL has significantly lower CD4 counts than those of NADL. There is an urgent and unmet need for uniform management guidelines for improving outcomes in this under-represented patient population. PMID: 31730692 [PubMed]
Source: Blood Research - Category: Hematology Tags: Blood Res Source Type: research
Conclusion Astroblastoma is an extremely rare CNS tumor. Morphological diagnosis is difficult, as the typical astroblastic rosettes may be present also in other CNS tumors, including some gliomas and ependymomas. In fact, AB can be considered as a morphologic pattern, which can be associated with a spectrum of molecular entities. Total resection is the best treatment; the precise role of chemotherapy and radiotherapy is still debated, particularly for high-grade tumors. We believe that DNA-methylation profiles represents an important instrument for confirming diagnosis, predicting prognosis and better defining the molec...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusion: The efficacy of brainstem gliomas—treated with CyberKnife is efficacious with mild toxicity. Introduction Brainstem gliomas (BSGs) account for 5–15% of brain tumors and more likely happen in children (1). BSGs constitute at least 20% of childhood brain neoplasms (2), and the peak age is 7–9 years. In contrast, BSGs is rare in the adult population and account for only 1.5–2.5% of brain glioma, with a peak age of 40–70 years (1). Diffuse intrinsic pontine glioma(DIPG) was the most common type of BSG is that could invade the whole brainstem including midbrain, pons as well as me...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, we have shown the safety and efficacy of Vemurafenib in a pediatric patient with DS affected by PXA. Ethics Statement This study was carried out in accordance with the recommendations of the Internal Review Board of the Bambino Gesù Children's Hospital with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Internal Review Board of the Bambino Gesù Children's Hospital. Informed Consent The authors declare that written informed consent was obtained from the pat...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Brain tumors are the most common malignancy of childhood. Approximately 50% of pediatric CNS tumors are astrocytomas, most low grade. Low grade glioma (LGG) are WHO grade I or II tumors. Pilocytic astrocytoma (PA) is the most common; accounts for 33% of all gliomas in children 0 –14 years and ∼18% of all childhood brain tumors. Prognosis with this slow-growing tumor is excellent; 10 year overall survival of ∼95%. However, event free survival averages ∼50%. Patient age and extent of tumor resection are key prognostic factors; tumor location and size impact resection and outcome.
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
Brain tumors are the most common solid tumor among children under 15, representing 20% of childhood cancers. Prognosis and therapeutic options vary dramatically based on histologic and molecular profiles. We have studied 222 brain tumors using the CHOP Comprehensive Solid Tumor Panel, which interrogates 238 cancer genes and 110 fusion partners. The most common tumors are pilocytic/pilomyxoid astrocytoma (67), medulloblastoma (23) and diffuse midline glioma (17). Clinically significant genomic alterations were identified in 93% of patients.
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
Brain tumors are the most common malignant solid tumor in pediatrics and as a whole are the leading cause of cancer related mortality in children. Our study encompasses the subgroup of childhood brain tumors that carry the highest mortality rate, high grade gliomas (HGG), i.e., glioblastoma multiforme, anaplastic astrocytoma grade III, diffuse intrinsic pontine glioma. Adult HGG are more common and have been studied more extensively than histologically similar tumors in children. Studies have confirmed adult and pediatric HGG are biologically different.
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
A remarkably rapidly expanding body of literature points to the epigenome as a new previously unsuspected mechanism of oncogenesis and another “hallmark of cancer.” Indeed, in a large number of cancers, aberrant epigenetic states occur through different mechanisms including altered DNA methylation, covalent histone modification, the reading of these histone modifications by protein regulation modules, histone exchange, chromatin remodelers, or via the effects of non-coding RNAs. Although mutations are also found in canonical signaling pathway genes, we and others identified chromatin-associated proteins to be m...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Mutational Landscape in Brain Tumors Source Type: research
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