{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BEND2 appears to be a multifunctional gene whose dysregulation contributes to distinct disease processes. In several central nervous system and soft‐tissue neoplasms, BEND2 functions as an oncogenic partner in gene fusions—such as EWSR1–BEND2, MN1–BEND2, and MAMLD1–BEND2—that are associated with tumors originally classified as astroblastomas and related high‐grade neuroepithelial neoplasms. These fusion events suggest that the BEND2 element may confer aberrant transcriptional regulation, thereby driving cellular transformation and influencing tumor phenotype, clinical outcome, and even gender predominance (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, loss‐of-function events involving BEND2 have been observed in patients with neurodevelopmental disorders; for example, microdeletions that include BEND2 along with adjacent genes (such as CDKL5) have been identified in individuals exhibiting Rett‐like features with early onset seizures."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, network analyses in the context of Parkinson’s disease have implicated BEND2 as one of several target genes of hsa‐miR‐142. In these studies, BEND2 was identified as part of a regulatory network potentially influencing disease progression, suggesting that even in neurodegenerative conditions, modulation of BEND2 expression may have biological significance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that aberrations of BEND2—whether through fusion-induced gain-of-function events in cancer or deletion-mediated loss-of-function in developmental disorders, as well as transcriptional regulation in neurodegeneration—point to its diverse roles in human disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emilija Todorovic, Brendan C Dickson, Ilan Weinreb "}, {"type": "b", "children": [{"type": "t", "text": "Salivary Gland Cancer in the Era of Routine Next-Generation Sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Head Neck Pathol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12105-020-01140-4"}], "href": "https://doi.org/10.1007/s12105-020-01140-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32124419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32124419"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Takeyoshi Tsutsui, Yoshiki Arakawa, Yasuhide Makino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spinal cord astroblastoma with EWSR1-BEND2 fusion classified as HGNET-MN1 by methylation classification: a case report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Tumor Pathol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10014-021-00412-3"}], "href": "https://doi.org/10.1007/s10014-021-00412-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34313881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34313881"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Akihiko Yoshida, Kaishi Satomi, Eisuke Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Soft-tissue sarcoma with MN1-BEND2 fusion: A case report and comparison with astroblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.23028"}], "href": "https://doi.org/10.1002/gcc.23028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35094441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35094441"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Débora Cabral de Carvalho Corrêa, Francine Tesser-Gamba, Indhira Dias Oliveira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular profiling of pediatric and adolescent ependymomas: identification of genetic variants using a next-generation sequencing panel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurooncol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11060-021-03848-x"}], "href": "https://doi.org/10.1007/s11060-021-03848-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34570300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34570300"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sabrina Rossi, Sabina Barresi, Giovanna Stefania Colafati, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Paediatric astroblastoma-like neuroepithelial tumour of the spinal cord with a MAMLD1-BEND2 rearrangement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropathol Appl Neurobiol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/nan.12814"}], "href": "https://doi.org/10.1111/nan.12814"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35301744"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35301744"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Norman L Lehman, Nathalie Spassky, Müge Sak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-022-29302-8"}], "href": "https://doi.org/10.1038/s41467-022-29302-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35440587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35440587"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Anna Burford, Alan Mackay, Sergey Popov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-19389-9"}], "href": "https://doi.org/10.1038/s41598-018-19389-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29348602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29348602"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nadia Bahi-Buisson, Benoit Girard, Agnes Gautier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epileptic encephalopathy in a girl with an interstitial deletion of Xp22 comprising promoter and exon 1 of the CDKL5 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30974"}], "href": "https://doi.org/10.1002/ajmg.b.30974"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19455595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19455595"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jack Kelly, Rana Moyeed, Camille Carroll, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic networks in Parkinson's and Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.102943"}], "href": "https://doi.org/10.18632/aging.102943"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32205467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32205467"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xiaoting Liu, Jinhu Chen, Tianyuan Guan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miRNAs and target genes in the blood as biomarkers for the early diagnosis of Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Syst Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12918-019-0680-4"}], "href": "https://doi.org/10.1186/s12918-019-0680-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30665415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30665415"}]}]}]}