ATRX gene codifies for a protein member of the SWI-SNF family and was cloned for the first time over 25 years ago as the gene responsible for a rare developmental disorder characterized by α-thalassemia and intellectual disability called Alpha Thalas...
ATRX is a chromatin remodeller that maintains telomere homeostasis. Loss of ATRX is described in approximately 10% of pancreatic neuroendocrine tumours (PanNETs) and associated with poorer prognostic features. Here, we present a genetically engineere...
The alpha-thalassemia mental retardation X-linked (ATRX) syndrome protein is a chromatin remodeling protein that primarily promotes the deposit of H3.3 histone variants in the telomere area. ATRX mutations not only cause ATRX syndrome but also influe...
Atrx loss was recently ascertained as insufficient to drive pancreatic neuroendocrine tumour (PanNET) formation in mice islets. We have identified a preponderant role of Atrx in the endocrine dysfunction in a Rip-Cre;AtrxKO genetically engineered mou...
Proliferating cells must enact a telomere maintenance mechanism to ensure genomic stability. In a subset of tumors, telomeres are maintained not by telomerase, but through a homologous recombination-based mechanism termed Alternative Lengthening of T...
Methyl-CpG binding protein 2 (MeCP2) is a multi-function factor involved in locus-specific transcriptional modulation and the regulation of genome architecture, e.g., pericentric heterochromatin (PCH) organization. MECP2 mutations are responsible for...
The Drosophila melanogaster dADD1 and dXNP proteins are orthologues of the ADD and SNF2 domains of the vertebrate ATRX (Alpha-Thalassemia with mental Retardation X-related) protein. ATRX plays a role in general molecular processes, such as regulating...
Whole genome and transcriptome sequencing of a cohort of 67 leiomyosarcomas has been revealed ATRX to be one of the most frequently mutated genes in leiomyosarcomas after TP53 and RB1. While its function is well described in the alternative lengtheni...
Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homol...
Adrenocortical carcinoma (ACC) is a rare malignancy that is associated with a dismal prognosis. Pan-genomic studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenocortical tumorigenesis. Our aims were to evaluate the protein expre...
High-grade glioma, including anaplastic astrocytoma and glioblastoma (GBM) patients, have a poor prognosis due to the lack of effective treatments. Therefore, the development of new therapeutic strategies to treat these gliomas is urgently required....
Herpes simplex virus 1 (HSV-1) transcribes its genome using host RNA polymerase II (Pol II) in a temporally regulated cascade. We previously proposed a model of Transient Immediate Early gene Mediated Repression (TIEMR), in which early repression of...
ATRX is an important molecular marker according to the 2021 WHO classification of adult-type diffuse glioma. We aim to predict the ATRX mutation status non-invasively using radiomics-based machine learning models on MRI and to determine which MRI seq...
The chromatin remodelling proteins DAXX and ATRX are key regulators of genome stability and epigenetic processes. Alterations in their expression have been associated with tumour stage and prognostic outcomes in various human cancer types, whereas th...
The chromatin-remodeling protein ATRX, which is currently recognized as one of the key genome caretakers, plays an important role in oogenesis and early embryogenesis in mammals. ATRX distribution in the nuclei of mouse embryos developing in vivo and...
Subsets of Neurofibromatosis Type 1 (NF1)-associated solid tumors have been shown to display high frequencies of ATRX mutations and the presence of alternative lengthening of telomeres (ALT). We studied the phenotype of combined NF1 and ATRX deficien...
Glioblastoma multiforme (GBM) is a type of brain tumor that is notorious for its aggressiveness and invasiveness, and the complete removal of GBM is still not possible, even with advanced diagnostic strategies and extensive therapeutic plans. Its dis...
Tumor cells are hallmarked by their capacity to undergo unlimited cell divisions, commonly accomplished either by mechanisms that activate TERT or through the alternative lengthening of telomeres pathway. Neuroblastoma is a heterogeneous pediatric ca...
Neuroblastoma (NB) is characterized by several malignant phenotypes that are difficult to treat effectively without combination therapy. The therapeutic implication of mitochondrial ClpXP protease ClpP and ClpX has been verified in several malignanci...
ATR-X syndrome is a rare X-linked congenital disorder caused by hypomorphic mutations in the ATRX gene. A typical phenotype is well defined, with cognitive impairment, characteristic facial dysmorphism, hypotonia, gastrointestinal, skeletal, urogenit...
Metastatic disease is linked to TERT promoter mutations in conjunctival melanomas (CM). Both TERT promoter and ATRX mutations are associated with faulty telomere maintenance. This study aimed to determine the prognostic value of ATRX loss in conjunct...
Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-m...
α-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in ATRX. An ATR-X model mouse lacking Atrx exon 2 displays phenotypes that resemble symptoms in the human intellectual disability: cognitive defects and abno...
During carcinogenesis, cells must acquire a telomere maintenance mechanism in order to avoid telomere shortening-induced replicative senescence. While most tumors activate telomerase, a minority of them employ a recombinational mechanism called Alter...
Background and Objectives: Glioblastoma (GBM) is among the most aggressive and lethal primary brain tumors, characterized by high heterogeneity, invasive growth, and resistance to conventional therapies. The 2021 WHO classification highlights the imp...
Hemoglobin disorders are among the most common inherited diseases worldwide. Their clinical manifestations range from anemia to more severe forms associated with neurological impairments. These complications can result as secondary consequences of th...
Introduction: A glioblastoma is an intra-axial brain tumour of glial origin that belongs to the category of diffuse gliomas and is the most common malignant neoplasia of the central nervous system. The rate of survival at 5 years, from the moment of...
Current knowledge on the molecular landscape of pancreatic neuroendocrine tumors (PanNETs) has advanced significantly. Still, the cellular origin of PanNETs is uncertain and the associated mechanisms remain largely unknown. DAXX/ATRX and MEN1 are the...
Background/Objectives: Astrocytoma, IDH-mutant, CNS WHO grade 3, is a diffuse glioma with poor prognosis, molecularly defined by IDH mutations and frequently co-occurring TP53 and ATRX alterations. This study aimed to delineate the genomic landscape...
Glioblastoma is considered the most aggressive tumor of the central nervous system. The tumor microenvironment includes several components, such as endothelial cells, immune cells, and extracellular matrix components like matrix metalloproteinase-9 (...
The Death-domain associated protein 6 (DAXX) is an evolutionarily conserved and ubiquitously expressed multifunctional protein that is implicated in many cellular processes, including transcription, cellular proliferation, cell cycle regulation, Fas-...
One of the main problems we face with PPGL is the lack of molecular markers capable of predicting the development of metastases in patients. Telomere-related genes, such as TERT and ATRX, have been recently described in PPGL, supporting the associati...
Glioblastoma is a solid, infiltrating, and the most frequent highly malignant primary brain tumor. Our aim was to find the correlation between sex, age, preoperative Karnofsky performance status (KPS), presenting with seizures, and extent of resectio...
Telomere maintenance plays important roles in genome stability and cell proliferation. Tumor cells acquire replicative immortality by activating a telomere-maintenance mechanism (TMM), either telomerase, a reverse transcriptase, or the alternative le...
Gliomas are differentiated into two major disease subtypes, astrocytoma or oligodendroglioma, which are then characterized as either IDH (isocitrate dehydrogenase)-wild type or IDH-mutant due to the dramatic differences in prognosis and overall survi...
Many exciting advances in cancer-related telomere biology have been made in the past decade. Of these recent advances, great progress has also been made with respect to the Alternative Lengthening of Telomeres (ALT) pathway. Along with a better under...
Pericentric heterochromatin (PCH) is a particular form of constitutive heterochromatin that is localized to both sides of centromeres and that forms silent compartments enriched in repressive marks. These genomic regions contain species-specific repe...
Uterine Leiomyosarcoma (uLMS) is by far the most common type of uterine sarcoma, characterized by an aggressive clinical course, a heterogeneous genetic profile and a very scarce response to cytotoxic chemotherapy. The genetic make-up of uLMS is an a...
Background: Grade 3 gastro-entero-pancreatic neuroendocrine tumors (G3 GEP-NET) are poorly characterized in terms of molecular features and response to treatments. Methods: Patients with G3 GEP-NET were included if they received capecitabine and temo...
Despite their low incidence, pediatric high-grade gliomas (pHGGs), including diffuse intrinsic pontine gliomas (DIPGs), are the leading cause of mortality in pediatric neuro-oncology. Recurrent, mutually exclusive mutations affecting K27 (K27M) and G...
Telomere maintenance enables unlimited cell proliferation by counteracting telomere erosion. While the majority of tumors activate telomerase, a significant subset—approximately 10–15%—utilizes alternative lengthening of telomeres (...
While loss-of-function mutations in the ATRX gene have been implicated as a driving force for a variety of pediatric brain tumors, as well as pancreatic neuroendocrine tumors, the role of ATRX in gene regulation and oncogenic development is not well-...
Herpesviruses are important pathogens that can cause significant morbidity and mortality in the human population. Herpesviruses have a double-stranded DNA genome, and viral genome replication takes place inside the nucleus. Upon entering the nucleus,...
In this review, we discuss the molecular characteristics, development, evolution, and therapeutic perspectives for pediatric high-grade glioma (pHGG) arising in cerebral hemispheres. Recently, the understanding of biology of pHGG experienced a revolu...
The study of the molecular pathways underlying cancer has given us important insights into how breaks in our DNA are repaired and the dire consequences that can occur when these processes are perturbed. Extensive research over the past 20 years has s...
Intramedullary spinal cord tumors (IMSCTs) harbor unique genetic mutations which may play a role in prognostication and management. To this end, we present the largest cohort of IMSCTs with genetic characterization in the literature from our multi-si...
Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I–IV (now 1–4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification...
Background/Objectives: Thalassemia, a hereditary blood disorder, leads to reduced hemoglobin levels, impairing oxygen transport and negatively impacting patient health. Recent research suggests a possible association between thalassemia and gastroint...
Glioma accounts for 80% of all malignant brain tumours and is the most common adult primary brain tumour. Age is an important factor affecting the development of cancer, as somatic mutations accumulate with age. Here, we aimed to analyse the signific...
Background: There is limited information regarding the immunohistochemistry stain and its prognostic role in adrenocortical carcinoma (ACC), and few studies focus on Asian patients. Our study aims to identify the correlation between immunohistochemis...
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