loading...| Preferred Name | Neuroblastoma | |
| Synonyms |
Organ_System: nervous system PathwayType: signaling CellType: cancer cell CellType: neural stem cell PMID: 12612655 PMID: 21295685 Description: Neuroblastoma (NB), the most common extracranial solid tumor in childhood, is derived from precursor cells of the peripheral (sympathetic) nervous system (neural crest neuroblasts). Pathway is built manually using published studies. Notes: Headnote: Neuroblastoma (NB), the most common extracranial solid tumor in childhood, is derived from precursor cells of the peripheral (sympathetic) nervous system (neural crest neuroblasts). Tumors are most frequently found in the adrenal medulla and paraspinal ganglia, but can arise anywhere along the sympathetic chain. Signaling description: MYCN amplification is found in about 22% of NB cases. Tumor suppressors including CHD5, MIR34A, and KIF1B may be affected due to a loss of the short arm of chromosome 1. TP53 or CDKN2A may be mutated in rare cases of NB and the amplification of MDM2, DDX1, and MYCL1 are found in small groups of NB. Activating germline mutations of ALK are responsible for the majority of hereditary NB cases. Moreover, ALK point mutations are often found in sporadic NB cases. Mutations in the PHOX2B gene have been observed in familial and sporadic forms of NB. NB patients with PHOX2B mutations also may have familial disorders of the neural crest such as Hirschsprung disease and congenital central hypoventilation syndrome. Sonic hedgehog (SHH) signaling is one of the key pathways in NB development. PTCH1, SMO, GLI1, and GLI2 were found to be overexpressed while GLI3 was found to be underexpressed. In addition, neurotrophin receptor signaling was found to be important in malignant transformation of sympathetic neuroblasts. The family of neurotrophin receptors includes neurotrophic tyrosine kinase receptor type 1, 2, and 3 (NTRK1/2/3). The ligands of NTRK involved in NB pathogenesis include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 and 4 (NTF3/4). These ligand-receptor interactions induce the PI3K/AKT1 and Ras/MAPK signaling. In addition to NGFs, other growth factors are also significant in the development of the sympathoadrenal lineage cells and transformed neuroblasts such as EGF, VEGFA, and IGF1/2. Lastly, the expression of neurogenic transcription factors including PHOX2A, PHOX2B, ASCL1, and HAND2 is controlled by bone morphogenetic proteins (BMP2/4/7) and Notch signaling. Outcome effects: The growth factor signaling in NB promotes cell survival and proliferation. The genetic rearrangements found in NB also result in the inhibition of apoptosis and activation of proliferation. In addition, constant SHH activation drives cell proliferation. Highlighted proteins: Proteins with increased expression or activity are highlighted in red, and proteins with decreased expression or activity are highlighted in blue. Mutated genes: Mutated genes are shown in white-out style. PMID: 19417027 Tissue: nerve tissue Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-c258812e-5720-43dd-ab31-5b90a1db677e PMID: 22430387 NodeType: Pathway Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 19622100 PMID: 15288262 Source: Diseases PMID: 22585002 PMID: 12438307 |
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| ID |
urn:agi-pathway:uuid-c258812e-5720-43dd-ab31-5b90a1db677e |
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| database_cross_reference |
PS:PathwayType PS:Description PS:Tissue PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Source |
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| has_exact_synonym |
Organ_System: nervous system PathwayType: signaling CellType: cancer cell CellType: neural stem cell PMID: 12612655 PMID: 21295685 Description: Neuroblastoma (NB), the most common extracranial solid tumor in childhood, is derived from precursor cells of the peripheral (sympathetic) nervous system (neural crest neuroblasts). Pathway is built manually using published studies. Notes: Headnote: Neuroblastoma (NB), the most common extracranial solid tumor in childhood, is derived from precursor cells of the peripheral (sympathetic) nervous system (neural crest neuroblasts). Tumors are most frequently found in the adrenal medulla and paraspinal ganglia, but can arise anywhere along the sympathetic chain. Signaling description: MYCN amplification is found in about 22% of NB cases. Tumor suppressors including CHD5, MIR34A, and KIF1B may be affected due to a loss of the short arm of chromosome 1. TP53 or CDKN2A may be mutated in rare cases of NB and the amplification of MDM2, DDX1, and MYCL1 are found in small groups of NB. Activating germline mutations of ALK are responsible for the majority of hereditary NB cases. Moreover, ALK point mutations are often found in sporadic NB cases. Mutations in the PHOX2B gene have been observed in familial and sporadic forms of NB. NB patients with PHOX2B mutations also may have familial disorders of the neural crest such as Hirschsprung disease and congenital central hypoventilation syndrome. Sonic hedgehog (SHH) signaling is one of the key pathways in NB development. PTCH1, SMO, GLI1, and GLI2 were found to be overexpressed while GLI3 was found to be underexpressed. In addition, neurotrophin receptor signaling was found to be important in malignant transformation of sympathetic neuroblasts. The family of neurotrophin receptors includes neurotrophic tyrosine kinase receptor type 1, 2, and 3 (NTRK1/2/3). The ligands of NTRK involved in NB pathogenesis include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 and 4 (NTF3/4). These ligand-receptor interactions induce the PI3K/AKT1 and Ras/MAPK signaling. In addition to NGFs, other growth factors are also significant in the development of the sympathoadrenal lineage cells and transformed neuroblasts such as EGF, VEGFA, and IGF1/2. Lastly, the expression of neurogenic transcription factors including PHOX2A, PHOX2B, ASCL1, and HAND2 is controlled by bone morphogenetic proteins (BMP2/4/7) and Notch signaling. Outcome effects: The growth factor signaling in NB promotes cell survival and proliferation. The genetic rearrangements found in NB also result in the inhibition of apoptosis and activation of proliferation. In addition, constant SHH activation drives cell proliferation. Highlighted proteins: Proteins with increased expression or activity are highlighted in red, and proteins with decreased expression or activity are highlighted in blue. Mutated genes: Mutated genes are shown in white-out style. PMID: 19417027 Tissue: nerve tissue PMID: 22430387 NodeType: Pathway Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 19622100 PMID: 15288262 Source: Diseases PMID: 22585002 PMID: 12438307 |
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| id |
urn:agi-pathway:uuid-c258812e-5720-43dd-ab31-5b90a1db677e |
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| label |
Neuroblastoma |
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| notation |
uuid-c258812e-5720-43dd-ab31-5b90a1db677e |
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| prefLabel |
Neuroblastoma |
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| treeView |
urn:agi-folder:nerve_tissue urn:agi-folder:nervous_system urn:agi-folder:neuroblastoma urn:agi-folder:n |
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| subClassOf |
urn:agi-folder:nerve_tissue urn:agi-folder:nervous_system urn:agi-folder:neuroblastoma urn:agi-folder:n |