Materiały źródłowe

• #1 Embryonal tumors – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/embryonal-tumor/cdc-20367985

  Embryonal tumors are growths of cells that happen in the brain. The growths involve cells that are left over from fetal development, called embryonal cells. […] Embryonal tumors start when embryonal cells develop changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] The cancer cells might form a mass called a tumor. The tumor can grow and press on parts of the brain. The cancer cells also can travel in the fluid that supports the brain and spine. This can spread the cancer to other parts of the brain and spinal cord. When cancer spreads, it’s called metastatic cancer.

• #1 Embryonal Tumors of the Central Nervous System in Children: The Era of Targeted Therapeutics

  https://www.mdpi.com/2306-5354/5/4/78

  Embryonal tumors (ET) of the central nervous system (CNS) in children encompass a wide clinical spectrum of aggressive malignancies. […] However, with the advances in genomic technology and the outpouring of biological data over the last decade, clear insights into the molecular heterogeneity of these tumors are now well delineated. […] The major subtypes of ETs of the CNS in children include medulloblastoma, atypical teratoid rhabdoid tumor (ATRT), and embryonal tumors with multilayered rosettes (ETMR), which are now biologically and clinically characterized as different entities. […] These important developments have paved the way for treatments guided by risk stratification as well as novel targeted therapies in efforts to improve survival and reduce treatment burden. […] Over the past decade, a surge genomic and epigenomic data on embryonal tumors of the central nervous system (CNS) in children has dramatically advanced the understanding of tumor biology, paving the way toward improved diagnostic, reclassification, and therapeutic approaches to these formidable malignancies.

• #1 Molecular mechanism and therapeutic strategies for embryonal tumors with multilayered rosettes in children (Review)

  https://www.spandidos-publications.com/10.3892/mco.2025.2825?text=fulltext

  Embryonal tumors with multilayered rosettes (ETMR) are relatively rare but highly aggressive intracranial tumors that mainly occur in children under four years of age. […] The present review discusses the molecular biological characteristics and treatment progress of ETMR to further elucidate the pathogenesis of ETMR and lay a foundation for molecular therapy of ETMR. […] ETMR are molecularly characterized by distinct DNA methylation signatures and dysregulated expression of oncogenic miRNAs. […] ETMR were distinguished from other pediatric intracranial tumors by analyzing DNA methylation and transcriptome sequencing data. […] ETMR are mainly driven by epigenetic mechanisms. […] C19MC amplification is the only major recurrent genomic alteration reported in ETMR to date. […] C19MC amplification and tumor suppressor p53 deletion are significant factors that drive undifferentiated hepatic embryonic sarcoma development.

• #1 Molecular mechanism and therapeutic strategies for embryonal tumors with multilayered rosettes in children (Review)

  https://www.spandidos-publications.com/10.3892/mco.2025.2825?text=fulltext

  DICER1 is considered the first ETMR susceptibility gene and a potential ETMR driver. […] The current treatment options for ETMR include maximum surgical excision and adjuvant chemotherapy, high-dose chemotherapy with stem cell salvage, and focal or whole-brain whole-spinal radiation therapy. […] However, current research on ETMR remains limited. […] The treatment of patients with ETMR has only slightly improved, and the five-year OS rate remains 30%. […] LIN28A is involved in regulating the development and self-renewal of embryonic stem cells as a post-transcriptional regulator affecting the maturation of miRNA. […] Cumulative studies discovered alternative targets for ETMR therapy. […] Despite the availability of various therapeutic strategies, ETMR remains a highly lethal disease.

• #1 Embryonal Tumors | Neupsy Key

  https://neupsykey.com/embryonal-tumors/

  The rapidly evolving molecular classification of brain tumors has fundamentally changed the understanding of embryonal neoplasms. […] The 2021 WHO classification recognizes two general categories of embryonal tumors: (1) Medulloblastoma (MB) (relatively common) and (2) other CNS embryonal tumors (rare). […] MB is not a single tumor entity but a heterogeneous cluster of multiple distinct, clinically relevant molecular subgroups. […] All MBs are designated CNS WHO grade 4 even though certain molecular groups and subgroups (e.g., WNT-activated tumors) have a good therapeutic response and cure is possible in some cases. […] MB is a genetically heterogeneous disease with five main molecular subgroups: (1) WNT-activated, (2) SHH-activated and TP53-wildtype, (3) SHH-activated and TP53-mutant, (4) non-WNT/non-SHH, group 3 and (5) non-WNT/non-SHH, group 4.

• #1 Other CNS Embryonal Tumors

  https://atlasgeneticsoncology.org/solid-tumor/209202

  Among embryonal tumors of the central nervous system (CNS), we primarily recognize the relatively common medulloblastoma which, by definition, arise from the cerebellum or dorsal brainstem. However, several rare other embryonal tumors which arise across the neuroaxis, are also contained within this group. […] Atypical teratoid/rhabdoid tumor (AT/RT) are genetically defined by somatic/germline mutations or losses of SMARCB1, a component of the SWI/SNF complex which functions to remodel chromatin. […] Other than recurrent SMARCB1 alterations, which arise in up to 95% of cases, AT/RT have remarkably quiet genomes. […] Epigenetic and transcriptional profiling have separated AT/RT into 3 distinct molecular subgroups: i) AT/RT-TYR, ii) AT/RT-SHH, and iii) AT/RT-MYC. […] Cribriform neuroepithelial tumor (CRINET) are defined by bi-allelic alterations impacting SMARCB1.

• #1 Other CNS Embryonal Tumors

  https://atlasgeneticsoncology.org/solid-tumor/209202

  Embryonal tumors with multilayered rosettes (ETMR) most commonly (~90%) harbor alterations of a microRNA cluster on chromosome 19q13.42 (C19MC) which includes high-level amplifications, fusions to TTYH1, and other rare gene rearrangements such as fusions to MYO9B or MIRLET7BHG. […] CNS neuroblastoma, FOXR2-activated are characterized by complex structural rearrangements that converge on FOXR2, an oncogenic transcription factor located on the X chromosome. […] These tumors are defined by a somatic internal tandem duplication (ITD) in BCOR resulting in increased expression and activation of the WNT signaling pathway. […] CNS embryonal tumor NEC/NOS is the classification used to describe a tumor with morphology consistent with other embryonal tumors, but lacking further molecular features to permit a more specific classification (not elsewhere classified, NEC) or failed a complete molecular workup (not otherwise specified, NOS).

• #1

  https://braintumourresearch.org/pages/types-of-brain-tumours-embryonal-tumours?srsltid=AfmBOoo8pm46JDKMT7-SvcPBDEb1ac7E4eggTngWEh6O_ZtUAoK241ET

  Embryonal brain tumours develop from cells left over from when the embryo was forming in the womb, but have remained in the brain after the child has been born. The cells should be harmless, but can sometimes become cancerous. […] This is an important step forward that enables clinicians to adapt existing treatments to the individual patients risk, and researchers to explore new ways to tackle these challenging tumours. […] Most embryonal tumours tend to be classified as grade 4, the most aggressive form of brain cancer, but very occasionally they may be classified as benign or slow-growing (low grade). […] In most cases, the cause of an embryonal tumour is not known. However there are certain inherited diseases that increase the risk of developing this type of tumour, including Turcot syndrome, Rubinstein-Taybi syndrome, Nevoid basal cell carcinoma (Gorlin) syndrome, Li-Fraumeni syndrome and Faconi anemia.

• #1 Embryonal tumors – Augusta HealthSearchClose SearchSearch IconSearch IconClose Search IconMobile Menu IconMobile Menu Close IconInstagramFacebookTwitterYoutube

  https://www.augustahealth.com/disease/embryonal-tumors/

  Embryonal tumors of the central nervous system are cancerous (malignant) tumors that start in the fetal (embryonic) cells in the brain. Embryonal tumors can occur at any age, but most often occur in babies and young children. […] Signs and symptoms of embryonal tumors vary, depending on the type of tumor, location, severity and other factors, such as pressure buildup within the brain. Symptoms may include, for example, headaches, nausea, vomiting, unusual tiredness, dizziness, double vision, unsteady walk, seizures or other issues. […] Treatment for embryonal tumors depends on the patient’s age (typically babies and young children), tumor type and location, tumor grade and extent, and other factors. Options include: […] Surgery to relieve fluid buildup in the brain. Some embryonal tumors may grow to block the flow of cerebrospinal fluid, which can cause a buildup of fluid that puts pressure on the brain (hydrocephalus).

• #1 MicroRNA Signatures as Biomarkers and Therapeutic Target for CNS Embryonal Tumors: The Pros and the Cons

  https://www.mdpi.com/1422-0067/15/11/21554

  Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients’ response to therapy is difficult to predict. […] However, the underlying molecular responses to genetic and environmental insults begin much earlier and microRNA (miRNA) networks are critically involved in these cellular regulatory mechanisms. […] It is encouraging to note that a great deal of progress has been made recently in dissecting miRNA pathways associated with the biology of embryonal brain tumors and a number of miRNAs have been identified as potential candidates for molecular therapeutic targets. […] Although therapeutical targeting of miRNAs has not yet been applied in clinical trials as single treatment agent regiments, it has recently been demonstrated both in vitro and in vivo that miRNA-targeted therapy may be useful in combination with conventional chemo-radiotherapy to sensitize cancer cells.

• #1 MicroRNA Signatures as Biomarkers and Therapeutic Target for CNS Embryonal Tumors: The Pros and the Cons

  https://www.mdpi.com/1422-0067/15/11/21554

  The class of genes that function as tumor suppressors and oncogenes in MB have recently been expanded to include the miRNA family. […] miR-124a was amongst the first to be characterized as a tumor suppressor miRNA in MB. […] miR-21 up-regulation is associated with metastasis and cell migration in a variety of solid tumors including breast, lung, colon, prostate, pancreas and stomach cancers, as well as brain tumors such as glioblastoma. […] Our lab recently reported the upregulation of miR-21 in MB cells, while miR-21 inhibition decreased MB cell migration in vitro. […] Metastases are responsible for the majority of MB-related mortality, yet our understanding of the molecular circuitry coordinating this process is fragmentary. […] miRNAs are believed to play a key role as suppressors or promoters of metastasis according to their mRNA targets.

• #1 Embryonal tumour with multilayered rosettes – Wikipedia

  https://en.wikipedia.org/wiki/Embryonal_tumour_with_multilayered_rosettes

  Embryonal tumor with multilayered rosettes (ETMR) is an embryonal central nervous system tumor. It is considered an embryonal tumor because it arises from cells partially differentiated or still undifferentiated from birth, usually neuroepithelial cells, stem cells destined to turn into glia or neurons. […] The main molecular characteristic of this tumor is amplification of the C19MC microRNA cluster, which is one of the largest miRNA clusters in the human genome, encoding 59 mature miRNAs expressed commonly in the placenta and in some embryonic stem cells. […] Molecular analysis of these tumors revealed that these tumors all shared many molecular features and thus comprise a single, molecularly-defined entity. […] Despite aggressive treatment, the prognosis is poor with 5-year overall survival rates less than 30%. Many patients show quick progression of disease, which is often refractory to treatment.

• #1 MicroRNA Signatures as Biomarkers and Therapeutic Target for CNS Embryonal Tumors: The Pros and the Cons

  https://www.mdpi.com/1422-0067/15/11/21554

  This review describes the current understanding of the roles of miRNAs in pediatric MB and AT/RT brain tumors, and highlights the advantages and the limitations of miRNAs as potential markers and therapeutic targets for MB and AT/RT. […] The important role of stem cells both in normal tissue and cancer development has driven much of the research into neural cancer stem cell biology. […] The research in this area has recently led to the identification of specific miRNA genes responsible for embryonal stem cells (ESCs) proliferation and differentiation and for the initiation and progression of cancer stem cells. […] With the knowledge that MB harbors cancer-initiating cells with stem cell properties, scientists are making a great effort to understand the involvement of aberrantly expressed miRNAs in embryonal cancer stem cells and to elucidate the mechanisms which distinguish these cells from normal stem cells.

• #1

  https://journals.lww.com/ijno/fulltext/2021/04001/diagnosis_and_management_of_central_nervous_system.28.aspx

  The clinical and histopathological characteristics of the tumor was first described by Bailey and Cushing, who hypothesized that the tumor took origin from medulloblasts which represent the multipotent stem cells of the neural tube. […] The understanding of these tumors has evolved over a period and now refined in the molecular era. […] During the past two decades, several researchers used high-throughput technologies including gene expression profiling, transcriptome, and DNA methylation profiling studies to stratify medulloblastoma into molecular subgroups which had prognostic significance. […] The biological heterogeneity of medulloblastoma is reflected in their molecular subgroups. […] The four recognized molecular subgroups are WNT-activated, SHH-activated, and non-WNT/non-SHH (Group 3 and Group 4).

• #1

  https://link.springer.com/article/10.1007/s11060-024-04667-6

  Central nervous system (CNS) embryonal tumors are a diverse group of malignant tumors typically affecting pediatric patients that recently have been better defined, and this paper describes evolution of a unique type of embryonal tumor at relapse. […] These two patients at diagnosis were classified as CNS embryonal tumors with EWSR1-PLAGL1 rearrangements based on histologic appearance and molecular data. At relapse both patients disease was reclassified as atypical teratoid rhabdoid tumor (ATRT) based on loss of INI-1, presence of SMARCB1 alterations, and methylation profiling results. […] CNS embryonal tumors with EWSR1-PLAGL1 rearrangements acquire or include a population of cells with SMARCB1 alterations that are the component that predominate at relapse, suggesting treatment aimed at this disease component at diagnosis should be considered.

• #1 Childhood Medulloblastoma and Other CNS Embryonal Tumors (PDQ®) – NCI

  https://www.cancer.gov/types/brain/hp/child-cns-embryonal-treatment-pdq

  An accurate diagnosis is critical for patients with embryonal tumors. […] Prognosis is poor for patients with medulloepithelioma and ETMR, with 5-year survival rates ranging between 0% and 30%. […] The 2021 WHO classification of embryonal tumors is as follows: Medulloblastoma, other CNS embryonal tumors, and pineoblastoma.

• #1 Methylation-based Subclassifications of Embryonal Tumor with Multilayered Rosettes in Not Just Pediatric Brains

  https://www.en-journal.org/journal/view.html?uid=642

  The aim of this study is to investigate the genetic profiles and methylation-based classifications of Embryonal tumor with multilayered rosettes (ETMR), with a specific focus on differentiating between C19MC amplified and C19MC-not amplified groups, including cases with DICER1 mutations. […] The underlying molecular biology of ETMR primarily involves the TTYH1:C19MC fusion and amplification of the C19MC oncogenic miRNA cluster, with the second most common driver being a hereditary mutation in the DICER1 gene. […] Next-generation sequencing (NGS) has proven valuable in diagnosing ETMR, and methylation clustering is also proving to be helpful, particularly in distinguishing ETMR from other primary CNS embryonal tumors. […] A key study by Lambo et al. revealed that while C19MC amplification is observed in 90% of ETMR cases, the next most common is DICER1 germline mutation, which conserved genomic instabilities due to R-loop structures as identified through whole genome sequencing.

• #1 Embryonal Tumors of the Central Nervous System in Children: The Era of Targeted Therapeutics

  https://www.mdpi.com/2306-5354/5/4/78

  These efforts to characterize MB have revolutionized our understanding of its pathogenesis and response to treatment, and will hopefully lead to improvements in survival and survivors’ quality of life. […] The significant heterogeneity of the biological drivers of these MB subtypes has impaired the development of a clinically applicable targeted approach. […] It is now evident that ATRT is an epigenetically driven disease, and thus targeting oncogenic drivers in epigenetic machinery is now the key focus of developmental therapeutics against these malignancies. […] Recent identification and description of molecular subclasses of ATRT should guide future risk-stratified and targeted therapeutic approaches with the intent of reducing toxicity and improving overall survival of these formidable tumors. […] Improved understanding of biological/molecular data aided by preclinical studies now provides avenues to render novel targeted therapies.

• #1 Clinicopathological and molecular characterization of a case classified by DNA‑methylation profiling as “CNS embryonal tumor with BRD4–LEUTX fusion” | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-023-01549-2

  Recent papers suggest that the bromodomain and extraterminal (BET) protein BRD4 could play an important role in the development of brain cancer. […] Therefore, BET bromodomain inhibitors blocking the bind between BRD4 and acetylated histones lead to transcriptional inactivation and have been reported to be promising therapeutic strategy in medulloblastomas and glioblastomas. […] Interestingly, in our case, loss of H3K27me3 expression was observed. […] These rare cases of CNS embryonal tumor characterized by BRD4LEUTX fusion need more clinical integration associated with prognosis to lead to an integration into the CNS WHO classification. […] Our case report suggested a new subgroup of CNS embryonal tumor with high aggressive potential, BRD4LEUTX fusion, loss of H3K27me3 protein expression, named Embryonal CNS tumor with BRD4LEUTX fusion.

• #1 Embryonal Tumors of the Central Nervous System in Children: The Era of Targeted Therapeutics

  https://www.mdpi.com/2306-5354/5/4/78

  The 2016 WHO classification integrated genetic information to already-existing histopathological data and has enabled more precise classification and diagnosis of these tumors. […] The critical issue is proper diagnosis of these entities, which would allow tailored therapy, including intensifying treatment for aggressive variants and de-escalating therapy for those tumors with better prognoses, in order to achieve long-term cures and minimizing treatment-related toxicity. […] The following section will discuss the major subtypes of pediatric embryonal tumors, which include MB, ATRT, and ETMR, their molecular biology, and the insights it provides in developing targeted therapies. […] Integrative genomic and methylomic studies over the past 15 years have shown that MB is not a single entity, but rather a heterogeneous group of diseases with unique clinical, molecular, and prognostic characteristics.

• #1 MicroRNA Signatures as Biomarkers and Therapeutic Target for CNS Embryonal Tumors: The Pros and the Cons

  https://www.mdpi.com/1422-0067/15/11/21554

  The investigation demonstrated that LC/A MB samples possess lower miR-9 expression compared to the other variants and that miR-9 under-expression is associated with poor prognosis in 34 patient samples of MB. […] The lower overall survival probability of patients with low miR-9 expression that also tends to have a more severe pathological grade suggests a strong trend towards prognostic significance. […] Despite the fact that miRNAs are involved in the tumorigenesis of a range of different tumors, the knowledge about the prognostic, diagnostic, and/or therapeutic target potential of these molecules in brain cancer, especially MBs, is still at an early stage. […] However, the true source of miRNAs in the body fluids and their exact secretory mechanism is still relatively unknown. […] The challenge remains to optimize and to validate miRNA biomarkers through carefully designed translational/clinical studies.

• #1 Molecular mechanism and therapeutic strategies for embryonal tumors with multilayered rosettes in children (Review)

  https://www.spandidos-publications.com/10.3892/mco.2025.2825

  DICER1 is considered the first ETMR susceptibility gene and a potential ETMR driver. […] The current treatment options for ETMR include maximum surgical excision and adjuvant chemotherapy, high-dose chemotherapy with stem cell salvage, and focal or whole-brain whole-spinal radiation therapy. […] LIN28A is involved in regulating the development and self-renewal of embryonic stem cells as a post-transcriptional regulator affecting the maturation of miRNA. […] Cumulative studies discovered alternative targets for ETMR therapy. […] Despite the availability of various therapeutic strategies, ETMR remains a highly lethal disease. […] These results highlight the limitations of these studies and the lack of prospective drug combination experiments. […] Therefore, it is necessary to improve understanding of the molecular biological changes in ETMR; further explore the relationship between C19MC amplification, DICER1 mutations, and the LIN28/let-7 pathway; determine the role of ubiquitination in ETMR as well as establish reasonable animal models; and provide possibilities for further treatment through reasonably designed targeted therapy and comprehensive preclinical trials.

• #1 Embryonal brain tumors – PubMed

  https://pubmed.ncbi.nlm.nih.gov/25415685/

  Embryonal brain tumors are a heterogeneous group of neoplasms that primarily occur in infants and young children. […] Emerging molecular data enable improved diagnostic and prognostic discrimination for these tumors. […] Because of their aggressive potential, they are treated similarly with multimodality therapy including maximal safe resection, chemotherapy, and age- and risk-adapted radiotherapy. […] It is hoped that the use of proton therapy for these vulnerable patients will translate into decreased long-term neurocognitive, endocrine, vascular, and developmental effects, in addition to a decreased risk of second malignancies.

• #2 Embryonal tumours | Brain and spinal cord tumours | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/brain-tumours/types/embryonal-tumours

  Embryonal tumours are brain tumours. They develop from cells that are left over from the early stages of our development. That is while we were still developing in our mothers womb. These cells are called embryonic cells. Normally these cells are harmless. But sometimes they can become cancerous. […] Embryonal tumours can start anywhere in the brain or the spinal cord. They are likely to grow quickly and can spread through the cerebrospinal fluid to other parts of the brain and the spinal cord (high grade tumour). […] Your treatment depends on the type of embryonal tumour you have and whether it has spread to other parts of the brain. The main treatments for embryonal tumours are: surgery, radiotherapy, chemotherapy. […] Radiotherapy uses high energy x-rays to destroy tumour cells. This reduces the risk of the embryonal tumour coming back. […] Chemotherapy uses cytotoxic drugs to kill tumours cells. It helps to reduce the risk of the tumour coming back or spread to other parts of the brain.

• #2 Embryonal Tumor: What It Is, Symptoms, Treatment & Prognosis

  https://my.clevelandclinic.org/health/diseases/embryonal-tumors

  An embryonal tumor is a type of brain tumor made up of fast-growing cells that are left over after fetal development (embryonic cells). […] Sometimes, extra embryonic cells remain in your childs brain after birth. This leads to the formation of embryonal tumors. […] A tumor happens when cells grow and divide more often than they should. Researchers arent sure why leftover embryonic cells turn into embryonal tumors. […] Treatment for embryonal tumors varies based on the type, size and location of the tumor. Common treatment options may include: Removal surgery, Radiation therapy, Chemotherapy, Targeted therapy (medications). […] Some embryonal tumors are aggressive, spread easily and can return after treatment. Others may be benign (noncancerous). Your childs healthcare provider will be able to give you the most accurate prognosis.

• #2 Embryonal Tumors of the Central Nervous System: An Update – PubMed

  https://pubmed.ncbi.nlm.nih.gov/32389264/

  Embryonal tumors of the central nervous system (CNS) are rare, high-grade neoplasms predominantly affecting the pediatric population. […] Although their prognosis is nearly uniformly poor, the rapidly evolving understanding of their molecular biology contributes to diagnosis, prognosis, treatment, and clinical trial participation. […] Knowledge of current tumor stratification and diagnostic techniques will help pathologists guide care and preserve tissue for necessary or desired additional testing.

• #2 Molecular mechanism and therapeutic strategies for embryonal tumors with multilayered rosettes in children (Review)

  https://www.spandidos-publications.com/10.3892/mco.2025.2825?text=fulltext

  DICER1 is considered the first ETMR susceptibility gene and a potential ETMR driver. […] The current treatment options for ETMR include maximum surgical excision and adjuvant chemotherapy, high-dose chemotherapy with stem cell salvage, and focal or whole-brain whole-spinal radiation therapy. […] However, current research on ETMR remains limited. […] The treatment of patients with ETMR has only slightly improved, and the five-year OS rate remains 30%. […] LIN28A is involved in regulating the development and self-renewal of embryonic stem cells as a post-transcriptional regulator affecting the maturation of miRNA. […] Cumulative studies discovered alternative targets for ETMR therapy. […] Despite the availability of various therapeutic strategies, ETMR remains a highly lethal disease.

• #2 Embryonal tumor with multilayered rosettes in a teenager

  https://www.redalyc.org/journal/5760/576069818029/html/

  The basis for unifying these distinct embryonal tumors is their expression of a common molecular signature, which is C19MC amplification and highly specific immunohistochemical staining for LIN28A. […] The presence of multilayered rosettes reactive for vimentin and the abundant neuropil reactive for synaptophysin prompted a diagnosis of embryonal tumor with abundant neuropil and true rosettes (ETANTR) and refined as embryonal tumor with multilayered rosettes, not otherwise specified (WHO Grade 4). […] Embryonal tumor with multilayered rosettes (ETMR) is a newly classified central nervous system embryonal tumor, which encompasses a heterogeneous group of highly aggressive malignant tumors. […] The diagnosis of ETMR can be made on the presence of C19MC amplification even if multilayered rosettes are not seen.

• #2 Rare brain embryonal tumors in infancy and early childhood | MedLink Neurology

  https://www.medlink.com/articles/rare-brain-embryonal-tumors-in-infancy-and-early-childhood

  Embryonal brain tumors account for approximately 13% of primary brain tumors of childhood, following gliomas as the second most common CNS tumor type in children up to 14 years of age. […] The World Health Organization 2021 Classification (WHO CNS5), based on an integrated taxonomy with a strong emphasis on molecular profiling, established two types of embryonal tumors: medulloblastomas and other CNS embryonal tumors. […] Rare embryonal tumors were previously classified as either medulloblastomas or supratentorial primitive neuroectodermal tumors sPNET, and they represent approximately 34% of all embryonal brain tumors of children and adolescents. […] Due to the unique features of the population affected by these entities, rare embryonal tumors deserve specific understanding, comprehensive diagnostic tools, and the development of much-needed novel tailored treatment approaches prioritizing less-toxic therapies to the immature nervous system.

• #2

  https://journals.lww.com/ijno/fulltext/2021/04001/diagnosis_and_management_of_central_nervous_system.28.aspx

  The clinical and histopathological characteristics of the tumor was first described by Bailey and Cushing, who hypothesized that the tumor took origin from medulloblasts which represent the multipotent stem cells of the neural tube. […] The understanding of these tumors has evolved over a period and now refined in the molecular era. […] During the past two decades, several researchers used high-throughput technologies including gene expression profiling, transcriptome, and DNA methylation profiling studies to stratify medulloblastoma into molecular subgroups which had prognostic significance. […] The biological heterogeneity of medulloblastoma is reflected in their molecular subgroups. […] The four recognized molecular subgroups are WNT-activated, SHH-activated, and non-WNT/non-SHH (Group 3 and Group 4).

• #2 Embryonal Tumors | Neupsy Key

  https://neupsykey.com/embryonal-tumors/

  Each of these subtypes has been further subdivided into distinctive molecular subgroups, adding more precision to patient-based risk stratification. […] Poor prognostic factors include metastatic disease at time of diagnosis, TP53 mutation, MYC amplification, non-WNT/non-SHH and LC/A histologies. […] AT/RT is a genetically defined tumor characterized by deletions and biallelic inactivating mutations of the SMARCB1 (a.k.a. hSNF5 or INI1) gene. […] Loss of the SMARCB1 protein in AT/RT results in unopposed expression of LIN28B (a key gene in embryonic development and for maintaining pluripotency in stem cells). […] Molecular profiling has identified three molecularly and clinically distinct AT/RT subgroups, currently designated as ATRT-TYR, ATRT-SHH, and ATRT-MYC.

• #2 Rare brain embryonal tumors in infancy and early childhood | MedLink Neurology

  https://www.medlink.com/articles/rare-brain-embryonal-tumors-in-infancy-and-early-childhood

  WHO CNS5 defines three main entities: embryonal tumor with multilayered rosettes (ETMR), CNS neuroblastoma FOXR2-activated, and CNS tumor with BCOR internal tandem duplication. […] ETMR is characterized by particularly aggressive behavior, with typical survival of 1 year after diagnosis despite intensive therapy and no consensus on treatment approach. […] ETMRs have few recurrent genetic aberrations, mainly affecting the microRNA (miRNA) pathway and including amplification of C19MC (ETMR, C19MC-altered) and mutually exclusive biallelic DICER1 mutations of which the first hit is typically inherited through the germline. […] The characteristic chromosome 19 miRNA cluster amplification of the 19q13.42 locus, named C19MC, was first described in 2009. […] C19MC is now considered the genetic hallmark of ETMRs, present in approximately 90% of all ETMRs regardless their histology.

• #2

  https://journals.lww.com/ijpm/fulltext/2022/65001/embryonal_tumors_in_the_who_cns5_classification__a.11.aspx

  Embryonal tumors are a heterogenous group of neoplasms mostly defined by recurrent genetic driver events. […] The application of DNA methylation/gene expression profiling in large series of neoplasms histologically defined as PNET, revealed tumors, which showed genetic events associated with glial tumors. […] The importance of molecular characteristics in CNS embryonal tumors is well represented by the identification of different molecular groups and subgroups in medulloblastoma. […] Among other embryonal tumors, two new recognized entities are introduced in CNS5: CNS neuroblastoma, FOXR2-activated, and CNS tumor with BCOR internal tandem duplication (ITD). […] The combination of histopathological and molecular features reflects the complexity of all these tumors and gives critical information in terms of prognosis and therapy.

• #2 Rare brain embryonal tumors in infancy and early childhood | MedLink Neurology

  https://www.medlink.com/articles/rare-brain-embryonal-tumors-in-infancy-and-early-childhood

  The introduction of increasingly specific tumor groups is an effort to create more internally homogeneous categories, to allow more precise prognostication, and potentially to develop targeted therapies. […] These tumors are characterized by a distinct DNA methylation profile harboring specific genetic alterations in the exon 15 within the BCOR gene. […] Optimal treatment strategies remain uncertain for this tumor entity.

• #2 Childhood Medulloblastoma & Other CNS Embryonal Tumors Treatment – NCI

  https://www.cancer.gov/types/brain/patient/child-cns-embryonal-treatment-pdq

  Medulloblastoma and other central nervous system (CNS) embryonal tumors may begin in embryonic (fetal) cells that remain in the brain after birth. […] Childhood medulloblastoma is caused by certain changes to the way brain cells function, especially how they grow and divide into new cells. Often, the exact cause of the cell changes is unknown. […] The risk for medulloblastoma is increased in people who have any of the following inherited diseases: Turcot syndrome, Rubinstein-Taybi syndrome, Nevoid basal cell carcinoma (Gorlin) syndrome, Li-Fraumeni syndrome, Fanconi anemia. […] Molecular testing checks for certain genes, proteins, or other molecules in a sample of tissue, blood, or bone marrow. Molecular tests also check for certain changes in a gene or chromosome that may cause or affect the chance of developing medulloblastoma, another type of embryonal tumor, or pineoblastoma.

• #2 Embryonal Tumors of the Central Nervous System in Children: The Era of Targeted Therapeutics

  https://www.mdpi.com/2306-5354/5/4/78

  The 2016 WHO classification integrated genetic information to already-existing histopathological data and has enabled more precise classification and diagnosis of these tumors. […] The critical issue is proper diagnosis of these entities, which would allow tailored therapy, including intensifying treatment for aggressive variants and de-escalating therapy for those tumors with better prognoses, in order to achieve long-term cures and minimizing treatment-related toxicity. […] The following section will discuss the major subtypes of pediatric embryonal tumors, which include MB, ATRT, and ETMR, their molecular biology, and the insights it provides in developing targeted therapies. […] Integrative genomic and methylomic studies over the past 15 years have shown that MB is not a single entity, but rather a heterogeneous group of diseases with unique clinical, molecular, and prognostic characteristics.

• #2

  https://link.springer.com/article/10.1007/s11060-024-04667-6

  Upon recurrence specimen analyzed for both patients had SMARCB1 alterations not identified at diagnosis while still retaining the EWSR1-PLAGL1 rearrangement. On immunohistochemistry both patients had INI-1 loss on recurrence which was not present at diagnosis. […] The SMARCB1 rearrangement could be acquired during treatment, but since the second patient had patchy INI-1 loss on IHC it could also be that these tumors are more susceptible to developing SMARCB1 alterations and a subset of cells in these tumors have this alteration at diagnosis and are the component most resistant to treatment. […] The fact that the disease for these two patients were assigned a different methylation class upon development of the SMARCB1 alterations at recurrence is notable. Change of DNA methylation class between primary and recurrent tumor is very unusual for brain tumors and this may represent one of the few exceptions and needs to be verified in larger cohort of patients.

• #2 Pathology Outlines – CNS embryonal tumor, NOS / NEC

  https://www.pathologyoutlines.com/topic/cnstumortumorembryotumNOS.html

  CNS embryonal tumors classified as NEC / NOS, like molecularly defined CNS embryonal tumors, are thought to arise from cells of neuroectodermal origin […] Molecular drivers for this diverse group of tumors are still not understood, either because the molecular profile does not fit a defined CNS WHO diagnostic entity (NEC) or molecular classification cannot be performed (NOS) […] Unknown at this time; may vary depending on the specific underlying genetic alterations […] Clinical presentation is nonspecific and depends on the location of the tumor […] Diagnosis of CNS embryonal tumor, NEC requires the exclusion of other CNS embryonal tumors with recurrent molecular alterations […] Diagnosis of CNS embryonal tumor, NOS applies to tumors where molecular testing cannot be performed […] Prognosis of CNS embryonal tumors is variable due to the molecular heterogeneity of this group of neoplasms and may actually be more favorable than originally understood due to the inclusion of molecularly defined high grade gliomas in the historic CNS PNET category […] Accurate molecular diagnosis is critical for an accurate prognosis […] No specific treatment can be offered for CNS embryonal tumors NOS / NEC in general […] If an unusual targetable mutation / fusion were identified in an NEC tumor, targeted therapy could be considered.

• #2

  https://journals.lww.com/ijno/fulltext/2021/04001/diagnosis_and_management_of_central_nervous_system.28.aspx

  Central nervous system (CNS) embryonal tumors exhibit significant biological heterogeneity and pose challenges in diagnosis and clinical management. […] Advances in understanding the molecular alterations of these tumors, using genomic and epigenomic platforms, have led to refinement in their diagnosis, classification, and guiding clinical management. […] Our understanding of embryonal tumors has evolved enormously since the initial recognition of these tumors. […] However, what has remained constant is the fact that embryonal tumors pose a challenge in diagnosis as well as management and are generally associated with a poor prognosis, excepting for an favorable biology observed in localized medulloblastoma, which has an excellent long-term survival. […] Understanding of the biology of embryonal tumors has exponentially grown, with the recognition of significant molecular heterogeneity within these embryonal tumors, resulting in the integration of molecular data in their classification in the WHO 2016 update classification of CNS tumors.

• #2 Clinicopathological and molecular characterization of a case classified by DNA‑methylation profiling as “CNS embryonal tumor with BRD4–LEUTX fusion” | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-023-01549-2

  Recent papers suggest that the bromodomain and extraterminal (BET) protein BRD4 could play an important role in the development of brain cancer. […] Therefore, BET bromodomain inhibitors blocking the bind between BRD4 and acetylated histones lead to transcriptional inactivation and have been reported to be promising therapeutic strategy in medulloblastomas and glioblastomas. […] Interestingly, in our case, loss of H3K27me3 expression was observed. […] These rare cases of CNS embryonal tumor characterized by BRD4LEUTX fusion need more clinical integration associated with prognosis to lead to an integration into the CNS WHO classification. […] Our case report suggested a new subgroup of CNS embryonal tumor with high aggressive potential, BRD4LEUTX fusion, loss of H3K27me3 protein expression, named Embryonal CNS tumor with BRD4LEUTX fusion.

• #2 ETMR Brain Cancer: Advancing Treatment Protocol – solvingkidscancer.org

  https://solvingkidscancer.org/blog/etmr-brain-cancer-advancing-treatment-protocol/

  Embryonal tumor with multilayered rosettes (ETMR) attacks the youngest, most vulnerable patients infants. […] This particular type of brain tumor is embryonal, which originates from the fetal (embryonic) cells in the brain. […] The exact cause of this pediatric cancer is unknown. Still, research shows that Since the discovery of the characteristic chromosome 19 miRNA cluster (C19MC) amplification over a decade ago, the methods for diagnosing this entity have improved and many new insights in the molecular landscape of ETMRs have been acquired. […] In fact, in 2019, he convened a congress of brain tumor experts to address the challenges of this pediatric brain tumor and has now developed the first treatment protocol with international collaboration. […] A consensus protocol was developed incorporating maximal safe surgical resection, induction chemotherapy with active pre-clinical agents, intrathecal chemotherapy, radiotherapy, and high-dose chemotherapy. […] This pioneering program also includes a robust data registry so research can advance at a more rapid pace to find a cure.

• #2 Childhood Medulloblastoma and Other CNS Embryonal Tumors (PDQ®) – NCI

  https://www.cancer.gov/types/brain/hp/child-cns-embryonal-treatment-pdq

  An accurate diagnosis is critical for patients with embryonal tumors. […] Prognosis is poor for patients with medulloepithelioma and ETMR, with 5-year survival rates ranging between 0% and 30%. […] The 2021 WHO classification of embryonal tumors is as follows: Medulloblastoma, other CNS embryonal tumors, and pineoblastoma.

• #3 Embryonal tumours | The Brain Tumour Charity

  https://www.thebraintumourcharity.org/brain-tumour-diagnosis-treatment/types-brain-tumour-children/embryonal-tumours/

  Embryonal tumours are brain tumours that develop from embryonic cells. These are cells left over from when we were growing in the womb as an embryo. […] Embryonal tumours are often high grade and are usually treated with either neurosurgery, radiotherapy, chemotherapy, or a combination of these. […] Embryonal tumours are brain tumours that develop from cells left over from when we are developing in the womb. These cells are called embryonic cells. They are usually harmless, but they can sometimes lead to a tumour starting. […] Not all embryonal tumours are cancerous. It depends on the type of tumour and how much it has developed. Most embryonal tumours tend to be diagnosed as Grade 4, which is considered to be cancerous. But, these tumours are sometimes diagnosed as low grade, which are considered benign.

• #3 Rare brain embryonal tumors in infancy and early childhood | MedLink Neurology

  https://www.medlink.com/articles/rare-brain-embryonal-tumors-in-infancy-and-early-childhood

  WHO CNS5 defines three main entities: embryonal tumor with multilayered rosettes (ETMR), CNS neuroblastoma FOXR2-activated, and CNS tumor with BCOR internal tandem duplication. […] ETMR is characterized by particularly aggressive behavior, with typical survival of 1 year after diagnosis despite intensive therapy and no consensus on treatment approach. […] ETMRs have few recurrent genetic aberrations, mainly affecting the microRNA (miRNA) pathway and including amplification of C19MC (ETMR, C19MC-altered) and mutually exclusive biallelic DICER1 mutations of which the first hit is typically inherited through the germline. […] The characteristic chromosome 19 miRNA cluster amplification of the 19q13.42 locus, named C19MC, was first described in 2009. […] C19MC is now considered the genetic hallmark of ETMRs, present in approximately 90% of all ETMRs regardless their histology.

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