Materiały źródłowe

• #1 Astrocytoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559042/

  Astrocytoma arises from astrocytes, the star-shaped glial cells found in the cerebrum. Constituting 60% of brain tumors, glial tumors include astrocytoma as the most prevalent form of glioma. […] The etiology of astrocytomas remains largely elusive, with ionizing radiation being the only well-established risk factor. Associations with other potential risk factors, such as electromagnetic fields, head injury, or occupational exposures, are not yet supported by conclusive evidence. […] The pathophysiology of astrocytoma involves the abnormal proliferation of astrocytes, glial cells that provide structural and metabolic support to neurons in the CNS. Multiple mechanisms result in the local effects of astrocytoma. These include direct invasion and competition for oxygen, leading to hypoxic injury to normal brain parenchyma. The tumor microenvironment, which includes interactions with other cell types, extracellular matrix components, and blood vessels, also influences tumor progression.

• #2 What is astrocytoma, and how is it different from glioblastoma? | MD Anderson Cancer Center

  https://www.mdanderson.org/cancerwise/what-is-astrocytoma–and-how-is-it-different-from-glioblastoma.h00-159694389.html

  Astrocytoma develops when astrocytes grow abnormally. Its not known exactly what causes an astrocytoma to form. Certain genetic mutations are associated with astrocytes growing out of control and becoming tumors. Still, scientists are not sure exactly what causes abnormal astrocyte growth. […] The precise causes are not known. Astrocytoma may be associated with certain genetic risk factors. Some hereditary syndromes, like Li-Fraumeni syndrome, Turcot syndrome, and von Hippel-Landau disease, may be connected to astrocytoma.

• #3 Astrocytoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283453-overview

  Astrocytomas are a form of glioma (ie, a neoplasm of the glial cells, which constitute the supportive tissue of the brain and nervous system). The predominant cell type in these tumors is thought to be derived from an immortalized astrocyte. […] Astrocytomas can be either well-circumscribed or diffusely infiltrating, which often drives the clinical manifestations, disease progression, treatment options, and prognosis. […] Regional effects of astrocytomas include compression, invasion, and destruction of brain parenchyma. Arterial and venous hypoxia, competition for nutrients, release of metabolic end products (eg, free radicals, altered electrolytes, neurotransmitters), and release and recruitment of cellular mediators (eg, cytokines) disrupt normal parenchymal function. Elevated intracranial pressure (ICP) attributable to direct mass effect, increased blood volume, or increased cerebrospinal fluid (CSF) volume may mediate secondary clinical sequelae.

• #4 Astrocytoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559042/

  Understanding the molecular and cellular mechanisms underlying astrocytoma development is essential for advancing diagnostic and therapeutic approaches. […] Genetic mutations and alterations in signaling pathways, such as the PI3K/AKT/mTOR and MAPK pathways, are often implicated in the uncontrolled growth and survival of these cells. These mutations can lead to the disruption of normal cellular processes, including cell cycle regulation, apoptosis, and differentiation.

• #5 Astrocytoma | Brain Tumor Program | Barrow Neurological InstituteSecond Opinion IconGroup 9Second Opinion IconGroup 9Group 49

  https://www.barrowneuro.org/condition/astrocytoma/

  Disruptions in normal cellular processes, like cell cycle regulation and DNA repair mechanisms, can contribute to tumor growth. So, too, do changes in the regulation of gene expression, like DNA methylation. […] Mutations to specific genes, such as TP53, TERT, EGFR, IDH1, IDH2, and ATRX, have been linked to astrocytoma development. These mutations can disrupt normal cell growth and division, leading to the uncontrolled growth of cancer cells. […] Some astrocytomas and other types of brain tumors have been linked to rare and inherited genetic conditions, like neurofibromatosis type I, Turcot syndrome, Lynch syndrome, or Li-Fraumeni syndrome. […] One of the few established environmental risk factors is exposure to high doses of ionizing radiation, such as radiation therapy from other cancers.

• #6 Astrocytoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283453-overview

  The etiology of diffuse astrocytomas has been the subject of analytic epidemiological studies that have yielded associations with various disorders and exposures. […] Biological investigation has found evidence that mutations in specific molecular pathways, such as the p53-MDM2-p21 and p16-p15-CDK4-CDK6-RB pathways, are associated with astrocytoma development and progression. […] The updated criteria emphasize the IDH mutational status as the primary molecular alteration used for stratification of adult-type diffuse gliomas, as mutations in either gene (IDH1 or IDH2) have been shown to alter disease progression, carry prognostic significance (the IDH1/2 mutation is associated with improved survival), and guide treatment decisions.

• #7 Astrocytoma | Brain and spinal cord tumours | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/brain-tumours/types/astrocytoma-glioblastoma-multiforme

  Astrocytomas develop from a type of glial cells called astrocytes. Astrocytes are star shaped cells. They support the nerve cells (neurones) in the brain. […] Doctors have changed the way they group and describe astrocytomas. All astrocytomas are now called: astrocytoma, IDH mutant. […] IDH (isocitrate dehydrogenase) is a gene. Your doctor looks for permanent changes (mutations) in the IDH gene. […] The grade depends on how the cells look. Generally, the more normal the cells look, the lower the grade. The more abnormal the cells look, the higher the grade. Grade also depends on genes and proteins in the tumour cells. […] There are 3 grades of IDH mutated astrocytomas: grade 2 (diffuse), grade 3 (anaplastic), grade 4. […] Your treatment depends on the grade of your astrocytoma. It also depends on whether you have changes (mutations) in certain genes.

• #8 Unraveling the signaling mechanism behind astrocytoma and possible therapeutics strategies: A comprehensive review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10598261/

  A form of cancer called astrocytoma can develop in the brain or spinal cord and sometimes causes death. A detailed overview of the precise signaling cascade underlying astrocytoma formation has not yet been revealed, although various factors have been investigated. Therefore, our objective was to unravel and summarize our current understanding of molecular genetics and associated signaling pathways with some possible therapeutic strategies for astrocytoma. […] All types of astrocytoma have a direct connection with some oncogenic signaling cascade. Common signaling is MAPK cascade, including RasRafERK, upregulated with activating EGFR/AKT/PTEN/mTOR and PDGFR. Recent breakthrough studies found that BRAF mutations, including KIAA1549: BRAF and BRAF V600E are responsible for astrocytoma progression. Additionally, cancer progression is influenced by mutations in some tumor suppressor genes, such as the Tp53/ATRX and MGMT mutant.

• #9

  https://link.springer.com/article/10.1007/s00401-015-1410-7

  Pilocytic astrocytomas (PAs) were recognized as a discrete clinical entity over 70 years ago. […] Until recently, almost nothing was known about the molecular mechanisms involved in their development. The use of high-throughput sequencing techniques interrogating the whole genome has shown that single abnormalities of the mitogen-activating protein kinase (MAPK) pathway are exclusively found in almost all cases, indicating that PA represents a one-pathway disease. The most common mechanism is a tandem duplication of a 2 Mb-fragment of #7q, giving rise to a fusion between two genes, resulting in a transforming fusion protein, consisting of the N-terminus of KIAA1549 and the kinase domain of BRAF. […] These molecular abnormalities will be reviewed, and the difficulties in their potential use in supporting a diagnosis of PA, when the histopathological findings are equivocal or in the choice of individualized therapy, will be discussed.

• #10 Unraveling the signaling mechanism behind astrocytoma and possible therapeutics strategies: A comprehensive review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10598261/

  In conclusion, cellular and molecular signaling is directly associated with the development of astrocytoma, and a combination of conventional and alternative therapies can improve the malignancy of cancer patients. […] The MAPK pathway, responsible for a variety of initiatives in the brain, including memory formation, pain perception, inducing cortical neurogenesis, and growth of the midbrain and cerebellum, corresponds to changes in the molecular origin. ERK transcription of ERK is essential for growth and their hyperactivation is a critical component in the emergence and spread of cancer. The most significant signaling cascade among the MAPK signal transduction pathways, the Ras/Ras/MAPK (MEK)/ERK pathway, is essential for the survival and growth of tumor cells. […] The mitogenactivated protein kinase (MAPK)/extracellular signalregulated kinase pathway leads to astrocytoma. More specifically, this signaling pathway may be altered in most patients with astrocytoma. For example, the activation of p38 MAPK is believed to be a potential oncogenic factor that promotes brain tumor growth and chemotherapy resistance in glioma cells by promoting tumor invasion and metastasis and being positively associated with tumor grade.

• #11 Unraveling the signaling mechanism behind astrocytoma and possible therapeutics strategies: A comprehensive review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10598261/

  Numerous genetic anomalies, most notably gene fusions between KIAA1549 and BRAF, have been shown to cause this dysregulation of the MAPK pathway. […] Several phosphorylation events and essential signaling elements of the MAPK pathway play an important role in carcinogenesis. Human cancer typically exhibits an alteration of the RASRAFMEKERKMAPK (RASMAPK) pathway as a result of aberrant receptor tyrosine kinase activation or gain of function mutations, mainly in the RAS or RAF genes. […] The BRAF protooncogene causes the most prevalent genomic distortion; cancers with duplication of BRAF showed increased mRNA levels of BRAF mRNA and a downstream target, CCND1, compared to tumors without duplication. […] The change in BRAF (V600E) is likely related to the extracerebellar region and the progression of diencephalic tumors.

• #12 Childhood Astrocytomas and Other Gliomas Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/brain/hp/child-astrocytoma-glioma-treatment-pdq

  This fusion is seen in most infratentorial and midline pilocytic astrocytomas but is present at lower frequency in supratentorial (hemispheric) tumors. […] Presence of the BRAF::KIAA1549 fusion is associated with improved clinical outcome (progression-free survival [PFS] and overall survival [OS]) in patients with pilocytic astrocytoma. […] Activating single nucleotide variants in BRAF, most commonly BRAF V600E, are present in a subset of pediatric gliomas and glioneuronal tumors across a wide spectrum of histologies, including pleomorphic xanthoastrocytoma, pilocytic astrocytoma, ganglioglioma, desmoplastic infantile ganglioglioma/astrocytoma, and others. […] Pediatric high-grade gliomas are biologically distinct from those arising in adults. […] Pediatric-type high-grade gliomas can be separated into distinct subgroups based on epigenetic patterns (DNA methylation).

• #13 Astrocytoma Tumors – AANS

  https://www.aans.org/patients/conditions-treatments/astrocytoma-tumors/

  Over the past 15 years, there have been important strides in understanding this disease, mainly derived from significant advances in the ability to study its genetic and biologic underpinnings […] IDH1 mutation is a fundamental feature that characterizes a subgroup of astrocytomas with mutation of a gene, called isocitrate dehydrogenase 1 (IDH1). This gene is involved in providing energy to the cells. Its mutation results in production of a chemical called 2-HG, which, over time, builds up inside the normal astrocytes and set them astray, causing astrocytomas. More than just another laboratory finding, this mutation is crucial because it characterizes almost 100% of low grade astrocytomas and is associated with significantly […] MGMT silencing has to do with the methylguanine-DNA methyltransferase (MGMT) enzyme involved in repairing DNA after it has been damaged by chemotherapics, thus protects the tumor against the action of these drugs. Certain astrocytomas have this enzyme turned off, and, as a result, they respond significantly better to chemotherapy with TMZ

• #14 Astrocytoma: What It Is, Causes, Symptoms, Types & Treatments

  https://my.clevelandclinic.org/health/diseases/17863-astrocytoma

  Astrocytomas are tumors that develop in your central nervous system (CNS) that grow from star-shaped astrocyte cells. […] Astrocytoma is the most common glioma. A glioma is a tumor that forms when glial cells grow out of control. […] Researchers dont know the exact cause of most astrocytomas. The majority of these tumors are sporadic, meaning that they happen randomly. […] However, recent studies have revealed that a mutation (change) in the IDH1 gene contributes significantly to the development of low-grade astrocytomas. This gene helps provide energy to your cells. Its mutation results in the production of a chemical called 2-HG, which, over time, builds up inside healthy astrocytes. This buildup causes the cells to become abnormal, causing astrocytomas. […] Exposure to ionizing radiation, such as from radiation therapy, increases your risk of developing astrocytoma.

• #15 Astrocytoma | Concise Medical Knowledge

  https://www.lecturio.com/concepts/astrocytoma/

  Several genetic mutations are associated with astrocytomas. […] Mutations in isocitrate dehydrogenase 1 (IDH1 gene) catalyze the reversible oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA) cycle. […] Mutations lead to production and buildup of a 2-hydroxyglutarate (2-HG): 2-HG inhibits enzymatic function of α-ketoglutarate (KG)-dependent dioxygenases, which are involved in DNA demethylation. […] 2-HG causes epigenetic dysregulation can lead to tumor development. […] Methylation of the methylguanine methyltransferase (MGMT) promoter silences expression of the gene. […] Inactivating p53 mutations are present in low-grade astrocytomas. […] Overexpression of platelet-derived growth factor alpha (PDGF-A) is also noted.

• #16 Astrocytoma: Insights into Risk Factors, Pathogenesis, Diagnosis and Management

  https://pubs.sciepub.com/jcrt/6/3/2/index.html

  Astrocytoma is one of the most common types of brain tumors. It arises from astrocytes-star-shaped cells that make up the glue-like or supportive tissue of the brain. There are different types and severities of Astrocytomas. According to (WHO),It can be classified into grades from I to IV. The most frequently diagnosed types of astrocytoma are pilocytic astrocytoma, grade II astrocytoma, anaplastic astrocytoma and glioblastoma multiforme. They may or may not be cancerous. The exact cause of astrocytoma is unknown. […] The diffuse astrocytoma (grade II) is the earliest stage of infiltrating astrocytic tumors. No premalignant stage of this tumor has been recognized. A high percentage of diffuse astrocytomas and anaplastic astrocytomas exhibit a characteristic mutation in the codon 132 of one copy of the IDH gene, with the most common mutation resulting in the substitution of histidine for arginine, and the acquired ability of the enzyme to catalyze the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of alpha-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). The accumulation of 2HG has been demonstrated in individuals with an inherited error in 2HG metabolism, a disease which is also associated with an increase in gliomas.

• #17 Astrocytoma: What It Is, Causes, Symptoms, Types & Treatments

  https://my.clevelandclinic.org/health/diseases/17863-astrocytoma

  The following rare genetic conditions are associated with the development of astrocytomas: […] Adjuvant therapy, sometimes called helper therapy, targets cancer cells that primary treatment didnt destroy. In the case of astrocytomas, surgery is the primary treatment. […] Grade 3 and grade 4 astrocytomas always require treatments other than surgery alone. Grade 2 astrocytomas may sometimes require adjuvant therapy. […] Chemotherapy involves medications that destroy cancer cells and/or prevent them from multiplying. Temozolomide (TMZ) is a drug that works by changing the DNA of tumor cells and, thus, causing the cells to die. TMZ is a first-line adjuvant therapy treatment for every grade 3 and grade 4 astrocytoma. […] Radiation therapy uses radiation (usually high-powered X-rays) to kill cancer cells. Its typically very effective in helping treat astrocytomas. […] The prognosis (outlook) of astrocytoma depends on several factors, including: […] The average survival rate varies depending on the grade of astrocytoma.

• #18 Glial tumors

  https://neuropathology-web.org/chapter7/chapter7bGliomas.html

  ATRX mutations have been reported in a large proportion of adult grade II and grade III astrocytomas, oligoastrocytomas, and secondary glioblastomas. […] Loss of the tumor suppressor gene PTEN on 10q as a result of deletion of 10q or the entire chromosome 10 is the most common genetic abnormality in glioblastoma, occurring in the majority of these tumors and less frequently in grade II and III astrocytomas. […] Overexpression of EGFR, on 7p, occurs in 40 % of glioblastomas and less frequently in lower grade astrocytomas and provides a potential target for EGFR inhibitors. […] An important epigenetic alteration in glioblastoma and other gliomas is silencing of the O6-methylguanine-DNA methyltransferase gene (MGMT) through hypermethylation of its promoter. […] Detection of many of the molecular changes that underlie the development of gliomas and other BT can now be done by immunohistochemistry and is getting into the mainstream of the diagnostic workup of BT.

• #19 Astrocytoma Tumors – AANS

  https://www.aans.org/patients/conditions-treatments/astrocytoma-tumors/

  Immunologic escape means that tumors escape the patrolling immune system, which normally destroys anything that is recognized as abnormal. Astrocytomas are among the tumors with the most developed ability to escape this surveillance. They do this by activating multiple genes that can turn the immune system off. There is consensus that counteracting this immune escape will result in important therapeutic benefits.

• #20

  https://link.springer.com/article/10.1007/s00401-015-1439-7

  Diffusely infiltrating astrocytomas include diffuse astrocytomas WHO grade II and anaplastic astrocytomas WHO grade III and are classified under astrocytic tumours according to the current WHO Classification. […] Recent advances in molecular genetics have uncovered that histopathologically diagnosed astrocytomas may consist of two genetically different groups of tumours. The majority of diffusely infiltrating astrocytomas regardless of WHO grade have concurrent mutations of IDH1 or IDH2, TP53 and ATRX. […] Those astrocytomas without IDH mutation tend to have a distinct genotype and a poor prognosis comparable to that of glioblastomas. […] A molecular classification may thus help delineate diffusely infiltrating astrocytomas into distinct pathogenic and prognostic groups, which could aid in determining individualised therapeutic strategies.

• #21 Low-Grade Astrocytoma: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1156429-overview

  In 2016, the WHO introduced molecular features into the classification of gliomas (IDH mutation and the deletion of 1p/19q) and paved the way to a growing amount of research lines. In the last few years, a great shift in our understanding of these tumors has taken place, and the standard diagnostic evaluation of gliomas must now include a molecular assessment. In fact, today we know that these molecular diagnostic markers are crucial for primary classification, which should be based primarily on mutational status rather than solely on histological grade. […] Another important distinction is between pediatric and adult low-grade astrocytomas. Pediatric low-grade astrocytomas exhibit markedly different molecular alterations, clinical course, and treatment than their adult counterpart. […] The molecular classification of low-grade diffuse gliomas has shown that some mutations correlate with survival. The median survival of patients with TP53 mutation with or without IDH1/2 mutation was significantly shorter than that for patients with 1p/19q loss with or without IDH1/2 mutation. Multivariate analysis with adjustment for age and treatment confirmed these results and revealed that TP53 mutation is a significant prognostic marker for shorter survival and 1p/19q loss for longer survival, while IDH1/2 mutations are not prognostic.

• #22 Glial tumors

  https://neuropathology-web.org/chapter7/chapter7bGliomas.html

  Neoplastic astrocytes share with normal ones the presence of intermediate cytoplasmic filaments. The protein of these filaments, glial fibrillary acidic protein (GFAP), can be detected by immunohistochemistry. […] Progress in the molecular biology of gliomas has revealed some correlation between molecular changes and grade. […] Beyond IDH mutations, the genetic lines of astrocytic and oligodendroglial tumors diverge. One subset of IDH1 mutant gliomas develop TP53 mutations and ATRX loss. These tumors evolve into DA, AA, and glioblastoma. […] IDH mutations may make tumor cells less viable by increasing their susceptibility to oxidative damage. […] TP53 mutations are common in diffuse astrocytoma, anaplastic astrocytoma, and secondary glioblastoma, and help distinguish glioma from gliosis.

• #23 Glial tumors

  https://neuropathology-web.org/chapter7/chapter7bGliomas.html

  ATRX mutations have been reported in a large proportion of adult grade II and grade III astrocytomas, oligoastrocytomas, and secondary glioblastomas. […] Loss of the tumor suppressor gene PTEN on 10q as a result of deletion of 10q or the entire chromosome 10 is the most common genetic abnormality in glioblastoma, occurring in the majority of these tumors and less frequently in grade II and III astrocytomas. […] Overexpression of EGFR, on 7p, occurs in 40 % of glioblastomas and less frequently in lower grade astrocytomas and provides a potential target for EGFR inhibitors. […] An important epigenetic alteration in glioblastoma and other gliomas is silencing of the O6-methylguanine-DNA methyltransferase gene (MGMT) through hypermethylation of its promoter. […] Detection of many of the molecular changes that underlie the development of gliomas and other BT can now be done by immunohistochemistry and is getting into the mainstream of the diagnostic workup of BT.

• #24 Astrocytoma – Wikipedia

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

  Astrocytoma causes regional effects by compression, invasion, and destruction of brain parenchyma, arterial and venous hypoxia, competition for nutrients, release of metabolic end products (e.g., free radicals, altered electrolytes, neurotransmitters), and release and recruitment of cellular mediators (e.g., cytokines) that disrupt normal parenchymal function. […] Homozygous deletion of CDKN2A/B is the main feature of high grade astrocytoma. In addition, a genome-wide pattern of DNA copy-number alterations (CNAs) has been uncovered, which is correlated with a patient’s survival and response to treatment. This pattern identifies among lower-grade astrocytoma patients a subtype, where the CNA genotype is correlated with an approximately one-year survival phenotype. […] Diagnosis of diffuse glioma, with astrocytomas mainly being diagnosed under IDH mutant and nuclear ATRX lost.

• #25 Diffuse astrocytoma – Libre Pathology

  https://librepathology.org/wiki/Diffuse_astrocytoma

  Diffuse astrocytoma (AKA: diffuse, low-grade astrocytoma) is a infiltrating astrocytoma occurring in the CNS white matter. […] Usually shows progression to glioblastoma sooner or later. […] IDH1 R132- or IDH2 R172-hotsopt mutations classify the tumors as Diffuse astrocytoma, IDH-mutant. […] Absence of LOH 1p/19q (otherwise classify tumor as oligodendroglioma). […] Tp53 mutations in approx. 60% (80-90% in gemistocytic, 50% in fibrillary types). […] CDKN2A/B homozygous deletion in IDH mutant diffuse astrocytoma has unfavourable prognosis. […] The existence of diffuse astrocytoma, IDH wildtype is challenged. […] Most adult cases show genetic alterations compatible with glioblastoma. […] Molecular upgrade according to cIMPACT-NOW Update 3 consensus (one of these is sufficient): EGFR amplification, Combined whole chromosome 7 gain and whole chromosome 10 loss (+ 7/ 10), TERT promoter mutation.

• #26 Isocitrate Dehydrogenase (IDH)-Mutant Astrocytoma | UCSF Brain Tumor Center

  https://braintumorcenter.ucsf.edu/condition/diffuse-astrocytoma-grade-ii

  IDH-mutant astrocytomas are graded based on how abnormal the tumor cells look under the microscope in addition to several other molecular alternations. Grade 3 IDH-mutant astrocytomas have more genetic alternations and anaplastic features, which include cell nuclei that are an irregular shape or size and more actively dividing cells. […] IDH-mutant astrocytomas with homozygous deletion of CDKN2A/B and/or have signs of lots of irregular blood vessels (microvascular proliferation) and necrosis (areas of dead tissue) are classified as grade 4. […] Typically, complete surgical removal of the tumor visible on the MRI offers the best patient outcomes for long-term survival. However, IDH-mutant astrocytoma can recur after surgery, so patients are regularly monitored for both tumor recurrence and progression to a higher-grade tumor. […] Grade 2 IDH-mutant gliomas are slow-growing tumors and hold a better prognosis than grade 3-4 IDH-mutant gliomas, which are high-grade gliomas, and progress more rapidly.

• #27

  https://link.springer.com/article/10.1007/s00401-015-1410-7

  In addition to the rare BRAF fusion variants described above (with a growing list of 5 partners), recurrent aberrations affecting the FGFR1 and NTRK family receptor kinases were observed. […] Interestingly, as indicated above, the spectrum of MAPK pathway alterations is not equal across all anatomic locations. The KIAA1549:BRAF fusion is extremely common in the cerebellum (found in approximately 90 % of cases) but somewhat less so supratentorially (although it is still very common).

• #28

  https://link.springer.com/article/10.1007/s00401-015-1410-7

  The NF1 protein, called neurofibromin, acts in the mitogen-activated protein (MAP) kinase pathway as a GTPase-activating protein for RAS, facilitating the deactivation of RAS. […] The common fusion rearrangement: The upper black box represents 7q34 on the long arm of chromosome 7. Both KIAA1549 and BRAF read towards the centromere (cent). A fragment of approximately 2 MB is duplicated and inserted at the breakpoint, producing a tandem duplication and the fusion between the 5 end of KIAA1549 and the 3 end of the BRAF gene that codes for the kinase domain. The fusion gene thus codes for the BRAF kinase domain together with the N-terminal part of KIAA1549, replacing the BRAF regulatory domain. […] The above alterations, identified in the era before next-generation sequencing, were together seen to account for the MAPK pathway hit in around 80-90 % of PAs.

• #29 Diffuse astrocytoma – Libre Pathology

  https://librepathology.org/wiki/Diffuse_astrocytoma

  Suggested Sign-out: Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV. […] WHO grade II diffuse gliomas IDH-wt/H3-wt in children and adolescents have an indolent clinical behavior and rare anaplastic progression. […] Most tumors show a BRAFV600E mutation, an FGFR alteration, or a MYB or MYBL1 rearrangement.

• #30 OR | The interplay mechanism between IDH mutation, MGMT-promoter methylation, and PRMT5 activity in the progression of grade 4 astrocytoma: unraveling the complex triad theory

  https://www.techscience.com/or/v32n6/56603

  The dysregulation of Isocitrate dehydrogenase (IDH) and the subsequent production of 2-Hydroxyglutrate (2HG) may alter the expression of epigenetic proteins in Grade 4 astrocytoma. The interplay mechanism between IDH, O-6-methylguanine-DNA methyltransferase (MGMT)-promoter methylation, and protein methyltransferase proteins-5 (PRMT5) activity, with tumor progression has never been described. […] Both IDH-mutant WHO grade 4 astrocytomas (n = 22, 64.7%) and IDH-wildtype glioblastomas (n = 12, 35.3%) had upregulated PRMT5 gene expression except in one case. […] There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma (p-value = 0.006). […] Specifically, IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation, who received only TMZ, have exhibited longer PFS.

• #31 OR | The interplay mechanism between IDH mutation, MGMT-promoter methylation, and PRMT5 activity in the progression of grade 4 astrocytoma: unraveling the complex triad theory

  https://www.techscience.com/or/v32n6/56603

  The relationship between PRMT5, MGMT-promoter, and IDH is not tri-directional. However, accumulation of D2-hydroxyglutarate (2-HG), which partially activates 2-OG-dependent deoxygenase, may not affect their activities. In IDH-wildtype glioblastomas, the 2HG-2OG pathway is typically inactive, leading to PRMT5 upregulation. […] Thus, using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.

• #32

  https://journals.lww.com/neur/fulltext/2016/64050/role_of_mtor_signaling_pathway_in_the_pathogenesis.32.aspx

  Subependymal giant cell astrocytomas (SEGA) are slow-growing benign intraventricular tumors, the pathogenesis of which is debated. Recent studies have shown that tuberous sclerosis complex (TSC) 1 and TSC2 genes are linked to the mammalian target of rapamycin (mTOR) cell signaling pathway. […] There is a definite role for TSC1 and TSC2 genes in the pathogenesis of SEGA as evidenced by loss of protein expression and presence of mutations. Strong expression of mTOR downstream signaling proteins indicates activation of mTOR pathway in these tumors, suggesting that proteins in this pathway may have the potential to serve as therapeutic targets in these patients. […] Mutations in TSC1 and TSC2 genes, and loss of proteins hamartin and tuberin play a definite role in the pathogenesis of SEGA. However, they are of limited value as diagnostic markers because loss of protein expression is not seen in all cases and analyzing TSC1 and TSC2 genes for mutation is not always feasible. mTOR pathway activation is a feature of SEGA, but its association with TSC gene alterations remains unclear and warrants further investigation to completely understand its role in the pathogenesis of these tumors.

• #33 Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex—Current Views on Their Pathogenesis and Management

  https://www.mdpi.com/2077-0383/12/3/956

  Cortical tubers, subependymal nodules (SENs) and SEGAs represent the main neuropathological lesions in patients with TSC. […] SENs are considered the precursor lesions of SEGAs. They are usually small lesions seen in over 90% of TSC patients in subependymal zones of lateral ventricles of the brain. It has been documented in multiple studies that non-calcified SENs may slowly transform into SEGAs. However, the exact moment of this transition is not fully defined. […] The pathogenesis of the transformation of SEN into SEGA is not yet fully understood. The concept that SEGAs develop from SEN is widely accepted, but the mechanisms underlying their progressive growth are unknown so far. One of the hypotheses says that it might be related to the location of SENs, as SEGAs most typically arise at the caudothalamic groove adjacent to the foramen of Monro. The increased flow of nutritional factors through the foramen of Monro may accelerate the growth of SEN and its transformation into SEGA. However, SEGA may also grow in other locations, especially in the third ventricle. The molecular background of SEGAs growth is also uncertain. Several studies evidenced a second-hit inactivation of TSC1 or TSC2 in SEGAs, suggesting that one contributor to SEGA development is the complete loss of a functional tuberin-hamartin complex and the subsequent mTORC1 activation. […] Currently, there is an increasing body of evidence that the transformation of SENs to SEGAs may be additionally triggered by the upregulation of genes related to the MAPK pathway.

• #34

  https://www.ouhsc.edu/pathologyJTY/OUMC/OUMC-COM/Com05/Com503-1-Diss.htm

  Pilomyxoid astrocytoma (PMA) is a recently described astrocytic neoplasm entity, which has not been included in the current (2000) World Health Organization (WHO) classification. This entity typically arises in the hypothalamus or optic chiasm of an infant or young child with the mean age of presentation from 10 to 18 months of age (range 2 – 84 month). Histologically, the salient features of PMA are rather monotonous, small, spindle bipolar cells with angiocentric arrangement within a strikingly myxoid background. The myxoid background material is positive for Alcian blue but negative for PAS. These features are well illustrated in our case. Atypical mitotic figures and substantial nuclear pleomorphism should not be seen. The angiocentric arrangement of tumor cells is another trap as it would suggest ependymoma. However, these arrangements are more irregular and fibrillar than the perivascular rosettes in ependymomas. Before PMA was recognized as a separate entity, these tumors were often considered as and treated as a variant of pilocytic astrocytoma. However, PMA has histological features that are quite unique and different from pilocytic astrocytomas. Most importantly, PMA behaves in a more aggressive manner than pilocytic astrocytomas. The specific combination of age, location and histological feature in PMAs is helpful in distinction between these two entities. It is worth to emphasize the importance of distinguishing between these two as the prognosis and treatment for each tumor differ.

• #35 Pathology of Cns Gemistocytic Astrocytoma Idh Mutant | Articl.net

  https://articl.net/resource/pathology-of-cns-gemistocytic-astrocytoma-idh-mutant

  Gemistocytic astrocytoma is a type of glioma characterized by the presence of gemistocyte-like astrocytes, and it is classified as an IDH-mutant diffuse astrocytoma according to the latest World Health Organization (WHO) classification of central nervous system (CNS) tumors. […] These tumors are considered Grade II and highlight the importance of isocitrate dehydrogenase (IDH) mutation in the pathogenesis and prognosis of gliomas. […] The majority of gemistocytic astrocytomas exhibit mutations in the IDH1 or IDH2 genes, which play a crucial role in the tumors metabolic pathway. The most common mutation is found in the IDH1 gene at the R132 position. […] The presence of IDH mutations is associated with a distinct metabolic signature (reduced -ketoglutarate levels) and influences tumor behavior and prognosis.

• #36 Pathology of Cns Gemistocytic Astrocytoma Idh Mutant | Articl.net

  https://articl.net/resource/pathology-of-cns-gemistocytic-astrocytoma-idh-mutant

  The presence of IDH mutations is generally associated with a better prognosis compared to IDH-wildtype gliomas. Overall survival rates are improved in patients with IDH-mutant astrocytomas, though the prognosis can still vary based on other genetic and clinical factors. […] Understanding these features is essential for accurate diagnosis and management, including considerations for surgical intervention and adjuvant therapies.

• #37 Clinical features and pathogenesis of scoliosis due to spinal astrocytoma

  https://www.spandidos-publications.com/10.3892/ol.2023.13726

  The present study investigated the effect of muscular imbalance on scoliosis by observing scoliosis caused by spinal astrocytomas. […] Overall, spinal astrocytomas can cause asymmetric destruction of the corresponding spinal cord segment, resulting in asymmetric atrophy and weakness of the multifidus muscle innervated by the spinal cord segment, thereby causing scoliosis that is convex to the weaker side. This mechanism involves asymmetric lower neuron paralysis of the multifidus muscle. […] Spinal astrocytoma is a malignant tumour that occurs in the spinal cord and causes damage to the neurological function of the corresponding segment of the spinal cord; it is unilateral in origin, visible on MRI and characterised by a clear length of involvement in the spinal cord. […] In this study, astrocytomas with unilateral initial symptoms were more likely to develop scoliosis, and the inferred tumour side was consistent with the convex side of scoliosis.

• #38 Clinical features and pathogenesis of scoliosis due to spinal astrocytoma

  https://www.spandidos-publications.com/10.3892/ol.2023.13726

  This confirms that asymmetrical weakness of the paraspinal muscles on one side is a cause of scoliosis, and the cause of muscle weakness is lower motor neuron paralysis due to spinal cord injury. […] The present study found that the essence of scoliosis caused by astrocytoma is lower neurone paralysis of the deep paravertebral muscles caused by spinal cord injury. […] In conclusion, spinal astrocytomas can cause lower neuron paralysis of the paraspinal multifidus muscles, which is innervated by the corresponding spinal cord segment affected by the tumour, resulting in scoliosis that is convex to the paralysed side. Astrocytoma-induced scoliosis is a type of scoliosis with several differences from idiopathic scoliosis.

• #39 Childhood Astrocytomas and Other Gliomas Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/brain/hp/child-astrocytoma-glioma-treatment-pdq

  The histone K27-altered cases occur predominantly in middle childhood (median age, approximately 10 years), are almost exclusively midline (thalamus, brain stem, and spinal cord), and carry a very poor prognosis. […] The 2021 WHO classification groups these cancers into a single entity: diffuse midline glioma, H3 K27-altered. […] However, there are clinical and biological distinctions between cases with H3.3 and H3.1 variants. […] The prognosis for H3.3 K27M patients is especially poor, with a median survival of less than 1 year; the 2-year survival rate is less than 5%. […] The 2021 WHO CNS grading scheme employs combined histological and molecular grading for many tumor types.

• #40 Unraveling the signaling mechanism behind astrocytoma and possible therapeutics strategies: A comprehensive review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10598261/

  Although the intrinsic signaling pathways targeted by phytochemicals in cancer treatment of cancer is still unknown, previous studies have shown that they can suppress both the STAT NFB, PIK/AKT, and MAPK signaling pathways and activate some genes that are responsible for tumor suppressor activity in a variety of cancer models. […] The accumulation of data suggests that many biological proteins, including cell cycle regulatory (cyclin B1, CDK1), apoptosis (Bax protein, Bcl2, caspase3, caspase9, 3 and ROS), tumor suppressor protein (p16, p21, p27, p38, and p53), signaling (pAkt, pmTOR, AMPK, PI3K/Akt, metastatic factor (MMP2 and MMP9) and growth factor receptor (VEGF, VEGFR2) are simultaneously targeted by some phytochemicals, which limit tumor formation.

• #41

  https://www.aurorahealthcare.org/services/neuroscience/brain-skull-base-care/brain-tumor/astrocytoma

  An astrocytoma is a type of glioma that starts growing from star-shaped cells in the brain or spine called astrocytes. Healthy astrocytes support nerve cells. […] Some types of astrocytomas are related to mutations in certain genes. […] The immune system has a process for limiting growth of cancer cells. Weve discovered that, for some astrocytomas, that immune process gets turned off. Researchers are confident that discovering a way to turn the immune system response back on will improve treatment of these types of astrocytomas.

• #42

  https://www.redalyc.org/journal/3935/393553808011/html/

  The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas […] IDH1/2 mutated gliomas have been associated with a better prognosis when compared to IDH-wildtype gliomas. […] Evidence suggests that IDH mutations lead to a hypermethylation phenotype and represent early events in tumoral transformation of the central nervous system (CNS) due to the production of the oncometabolite 2-hydroxyglutarate. […] IDH mutations can also be found in cartilaginous tumors, prostate cancer, acute lymphoblastic leukemia, acute myelogenous leukemia, and cholangiocarcinoma. […] IDH mutation can be associated with neoplastic transformation of CNS due to the synthesis of 2-hydroxyglutarate, a possible oncometabolite. […] IDH-mutant gliomas are associated with a better prognosis, WHO grade II tumors, younger patients, secondary GBMs, frontal lobe location, GCIMP phenotype, presence of MGMT methylation, and proneural gene expression. […] Target drugs able to suppress the oncometabolite 2-hydroxyglutarate can be the future adjuvant therapeutic modality.

• #43 Astrocytoma | Nationwide Children’s Hospital

  https://www.nationwidechildrens.org/conditions/astrocytoma

  A child may have short- and long-term complications from the tumor or treatment. […] Improving the quality of life for survivors of brain and spine tumors is an area of much ongoing research and continued progress. […] Nationwide Childrens Hospital is also a national leader in oncology research and clinical trials. […] There are many ongoing research studies aimed at improving outcomes for children and young adults with brain/spine tumorsunderstanding why these tumors develop and how to appropriately target them.

• #44 Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice

  https://www.jove.com/t/51763/modeling-astrocytoma-pathogenesis-vitro-vivo-using-cortical

  Phenotypically wild-type astrocytes and neural stem cells harvested from mice engineered with floxed, conditional oncogenic alleles and transformed via viral Cre-mediated recombination can be used to model astrocytoma pathogenesis in vitro and in vivo by orthotopic injection of transformed cells into brains of syngeneic, immune-competent littermates. […] Current astrocytoma models are limited in their ability to define the roles of oncogenic mutations in specific brain cell types during disease pathogenesis and their utility for preclinical drug development. […] Better astrocytoma models are required to define the role of specific combinations of mutations in particular cell types during astrocytoma pathogenesis. […] The role of initiating cell type and co-occurring mutations in astrocytoma pathogenesis are difficult to determine using established human GBM cell lines or PDX because they are derived from end-stage tumors that have accumulated extensive genetic mutations in undefined cell types during the course of malignant progression.

• #45 Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice

  https://www.jove.com/t/51763/modeling-astrocytoma-pathogenesis-vitro-vivo-using-cortical

  Thus, the influence of specific genetic mutations and cell type on cellular and molecular phenotypes can be determined in vitro and in vivo. […] The microenvironmental influence of brain region or developmental age on gliomagenesis can be determined by orthotopically injecting nGEM cells in different locations or in different aged mice. […] Thus, nGEM astrocytoma models with transformed cortical astrocytes and NSC are a valuable model system to determine the functional consequences of combinations of oncogenic mutations in specific cell types and may be useful in preclinical drug testing.

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