Clinical Characteristics and Outcomes of Central Nervous System Tumors Harboring NTRK Gene Fusions.

Purpose: Tropomyosin receptor kinase (TRK) fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients.

Experimental Design: We conducted an international retrospective cohort study of patients with TRK fusion-driven central nervous system tumors.

Fibromyxoid aSoft Tissue Tumor With PLAG1 Fusion-The First Case in an Adult Patient.

With the expanding possibilities of human genome research in recent years, the number of cases of soft tissue tumors that we are able to classify into the correct subgroups and to reveal their molecular profile is increasing. Among such tumors, we can also consider neoplasms that have a specific fusion of genes, in our case namely the pleomorphic adenoma gene 1 (PLAG1) and its partner. PLAG1 gene fusions were previously associated mainly with salivary gland pleomorphic adenomas, lipoblastomas, myoepithelial tumors, uterine epitheloid, myxoid leiomyosarcomas, and, recently, with PLAG1-rearranged fibromyxoid soft tissue tumors.

Novel and unusual fusion partners in aneurysmal bone cyst and their role in pathogenesis and histopathological evaluation of this disease.

Aims: The purpose of this study is to report novel and unusual fusion partners in aneurysmal bone cysts (ABCs). These findings may be useful in routine diagnostics as well as in studying the biology of -related disorders.

Methods: A cohort of seven patients diagnosed with ABC examined between 2014 and 2023 at Motol University Hospital in Prague was included into this retrospective non-randomised study.

Clinical and molecular study of radiation-induced gliomas.

In this study, we provide a comprehensive clinical and molecular biological characterization of radiation-induced gliomas (RIG), including a risk assessment for developing gliomas. A cohort of 12 patients who developed RIG 9.5 years (3-31 years) after previous cranial radiotherapy for brain tumors or T-cell acute lymphoblastic leukemia was established.

A 5-year-old boy with super-refractory status epilepticus and RANBP2 variant warranting life-saving hemispherotomy.

Focal cortical dysplasia (FCD) represents the most common cause of drug-resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug-resistant epilepsy evolving in super-refractory status epilepticus.

Genetic testing in children enrolled in epilepsy surgery program. A real-life study.

Objective: Although genetic causes of drug-resistant focal epilepsy and selected focal malformations of cortical development (MCD) have been described, a limited number of studies comprehensively analysed genetic diagnoses in patients undergoing pre-surgical evaluation, their outcomes and the effect of genetic diagnosis on surgical strategy.

Methods: We analysed a prospective cohort of children enrolled in epilepsy surgery program over January 2018-July 2022. The majority of patients underwent germline and/or somatic genetic testing.

Changes on chromosome 11p15.5 as specific marker for embryonal rhabdomyosarcoma?

Rhabdomyosarcomas (RMS) constitute a heterogeneous spectrum of tumors with respect to clinical behavior and tumor morphology. The paternal uniparental disomy (pUPD) of 11p15.5 is a molecular change described mainly in embryonal RMS.

Mazabraud's syndrome: A case report supported by molecular studies and review of the literature.

Mazabraud's syndrome represents rare benign disorder characterized by simultaneous occurrence of fibrous dysplasia of bone and intramuscular myxomas within surrounding soft tissue. Mutations of gene were proven to be causative for this condition. Here, we present a case report of a patient with unusual manifestation of this disease, who developed a pathological fracture of the femur in the setting of monostotic fibrous dysplasia.

Unusual case of inflammatory rhabdomyoblastic tumor in a pediatric patient.

Inflammatory rhabdomyoblastic tumor (IRMT) is a rare, recently described skeletal muscle neoplasm of uncertain malignant potential. We report an unusual tumor in the right arm of a 5-year-old boy, which is the first case of a pediatric IRMT. Immunohistochemically, most cells in the tumor were positive for CD163 and CD68 staining.

DIPG-like MYB-altered diffuse astrocytoma with durable response to intensive chemotherapy.

Pontine gliomas represent difficult to treat entity due to the location and heterogeneous biology varying from indolent low-grade gliomas to aggressive diffuse intrinsic pontine glioma (DIPG). Making the correct tumor diagnosis in the pontine location is thus critical. Here, we report a case study of a 14-month-old patient initially diagnosed as histone H3 wild-type DIPG.

Primary cardiac lipoblastoma of the right atrium.

Lipoblastoma is a rare neoplasm of the embryonal white fat. It occurs most commonly in children under the age of 3 years and usually inflicts the superficial soft tissues of trunk and extremities. We present the case of a 3-year-old male patient with a successfully resected primary cardiac right-atrial lipoblastoma with COL1A2::PLAG1 gene fusion.

Unusual fusion gene rearrangements in patients with nodular fasciitis: a study of rare and novel USP6 fusion partners with a review of the literature.

Aims: This retrospective non-randomised study aims to identify new and rare fusion partners with in the setting of nodular fasciitis. It has been proven, that nodular fasciitis can harbour different variants of fusions, which can be used in routine diagnostics and even determine the biological behaviour of the process.

Methods: A total of 19 cases of nodular fasciitis examined between 2011 and 2022 at Motol University Hospital in Prague were included into this study.

Genetic Testing for Malformations of Cortical Development: A Clinical Diagnostic Study.

Background And Objectives: Malformations of cortical development (MCD), though individually rare, constitute a significant burden of disease. The diagnostic yield of next-generation sequencing (NGS) in these patients varies across studies and methods, and novel genes and variants continue to emerge.

Methods: Patients (n = 123) with a definite radiologic or histopathologic diagnosis of MCD, with or without epilepsy were included in this study.

Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the Gene.

Background And Objectives: The gene, located at chromosome Xp11.23, encodes for a uridine diphosphate-galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somatic gene variants.

Prenatal and perinatal phthalate exposure is associated with sex-dependent changes in hippocampal miR-15b-5p and miR-34a-5p expression and changes in testicular morphology in rat offspring.

MicroRNAs are a large group of non-coding nucleic acids, usually 20-22 nt long, which bind to regulatory sections of messenger RNA (mRNA) and inhibit gene expression. However, genome activity is also regulated by hormones. Endocrine disruptors such as those from the phthalate group imitate or block these hormonal effects, and our previous study showed a long-lasting decrease in plasma testosterone levels in rat offspring exposed to a mixture of three phthalates and postnatally.

A rational approach to the CNS tumors diagnostics.

The new WHO classification of CNS tumors is largely based on molecular diagnostic. Without molecular methods some entities can no longer be diagnosed. We are trying to show a rational approach to the CNS tumors diagnostics, which is based on conventional molecular methods such as RT-PCR, Sanger sequencing, MLPA, extended by the next generation sequencing (NGS) and methylation SNP array.

Integrated genomic analysis reveals actionable targets in pediatric spinal cord low-grade gliomas.

Gliomas are the most common central nervous tumors in children and adolescents. However, spinal cord low-grade gliomas (sLGGs) are rare, with scarce information on tumor genomics and epigenomics. To define the molecular landscape of sLGGs, we integrated clinical data, histology, and multi-level genetic and epigenetic analyses on a consecutive cohort of 26 pediatric patients.

Clinicogenomic associations in childhood Langerhans cell histiocytosis: an international cohort study.

Langerhans cell histiocytosis (LCH) is a rare neoplastic disorder caused by somatic genetic alterations in hematopoietic precursor cells differentiating into CD1a+/CD207+ histiocytes. LCH clinical manifestation is highly heterogeneous. BRAF and MAP2K1 mutations account for ∼80% of genetic driver alterations in neoplastic LCH cells.

Effect of 17β-estradiol on the daily pattern of ACE2, ADAM17, TMPRSS2 and estradiol receptor transcription in the lungs and colon of male rats.

Covid-19 progression shows sex-dependent features. It is hypothesized that a better Covid-19 survival rate in females can be attributed to the presence of higher 17β-estradiol (E2) levels in women than in men. Virus SARS-CoV-2 is enabled to enter the cell with the use of angiotensin converting enzyme 2 (ACE2).

Survival and functional outcomes in paediatric thalamic and thalamopeduncular low grade gliomas.

Background: Childhood thalamopeduncular gliomas arise at the interface of the thalamus and cerebral peduncle. The optimal treatment is total resection but not at the cost of neurological function. We present long-term clinical and oncological outcomes of maximal safe resection.