Gastroblastoma with a novel EWSR1-CTBP1 fusion presenting in adolescence.
CTBP1
EWSR1
Wiskott-Aldrich syndrome
epithelial-mesenchymal transition
gastroblastoma
stomach
Journal
Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
17
05
2021
received:
03
04
2021
accepted:
22
05
2021
pubmed:
28
5
2021
medline:
19
3
2022
entrez:
27
5
2021
Statut:
ppublish
Résumé
Gastroblastomas are rare tumors with a biphasic epithelioid/spindle cell morphology that typically present in early adulthood and have recurrent MALAT1-GLI1 fusions. We describe an adolescent patient with Wiskott-Aldrich syndrome who presented with a large submucosal gastric tumor with biphasic morphology. Despite histologic features consistent with gastroblastoma, a MALAT1-GLI1 fusion was not found in this patient's tumor; instead, comprehensive molecular profiling identified a novel EWSR1-CTBP1 fusion and no other significant genetic alterations. The tumor also overexpressed NOTCH and FGFR by RNA profiling. The novel fusion and expression profile suggest a role for epithelial-mesenchymal transition in this tumor, with potential implications for the pathogenesis of biphasic gastric tumors such as gastroblastoma.
Substances chimiques
DNA-Binding Proteins
0
EWSR1 protein, human
0
Oncogene Proteins, Fusion
0
RNA-Binding Protein EWS
0
Alcohol Oxidoreductases
EC 1.1.-
C-terminal binding protein
EC 1.1.1.-
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
640-646Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Graham RP, Nair AA, Davila JI, et al. Gastroblastoma harbors a recurrent somatic MALAT1-GLI1 fusion gene. Mod Pathol. 2017;30(10):1443-1452.
Miettinen M, Dow N, Lasota J, Sobin LH. A distinctive novel epitheliomesenchymal biphasic tumor of the stomach in young adults ("gastroblastoma"): a series of 3 cases. Am J Surg Pathol. 2009;33(9):1370-1377.
Shin DH, Lee JH, Kang HJ, et al. Novel epitheliomesenchymal biphasic stomach tumour (gastroblastoma) in a 9-year-old: morphological, ultrastructural and immunohistochemical findings. J Clin Pathol. 2010;63(3):270-274.
Wey EA, Britton AJ, Sferra JJ, Kasunic T, Pepe LR, Appelman HD. Gastroblastoma in a 28-year-old man with nodal metastasis: proof of the malignant potential. Arch Pathol Lab Med. 2012;136(8):961-964.
Fernandes T, Silva R, Devesa V, Lopes JM, Carneiro F, Viamonte B. AIRP best cases in radiologic-pathologic correlation: gastroblastoma: a rare biphasic gastric tumor. Radiographics. 2014;34(7):1929-1933.
Ma Y, Zheng J, Zhu H, et al. Gastroblastoma in a 12-year-old Chinese boy. Int J Clin Exp Pathol. 2014;7(6):3380-3384.
Toumi O, Ammar H, Korbi I, et al. Gastroblastoma, a biphasic neoplasm of stomach: a case report. Int J Surg Case Rep. 2017;39:72-76.
Castri F, Ravegnini G, Lodoli C, et al. Gastroblastoma in old age. Histopathology. 2019;75(5):778-782.
Centonze G, Mangogna A, Salviato T, et al. Gastroblastoma in adulthood-a rarity among rare cancers-a case report and review of the literature. Case Rep Pathol. 2019;2019:4084196.
Nogueira Pinto D, Ventura J, Gomes D, et al. Gastroblastoma described in adult patient. Int J Case Rep Images. 2019;10:100995Z100901DP102019.
Candotti F. Clinical manifestations and pathophysiological mechanisms of the Wiskott-Aldrich syndrome. J Clin Immunol. 2018;38(1):13-27.
Cory GO, Garg R, Cramer R, Ridley AJ. Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich syndrome protein. J Biol Chem. 2002;277(47):45115-45121.
Taylor MD, Sadhukhan S, Kottangada P, et al. Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in human Wiskott-Aldrich syndrome. Sci Transl Med. 2010;2(37):37ra44.
Schrank BR, Aparicio T, Li Y, et al. Nuclear ARP2/3 drives DNA break clustering for homology-directed repair. Nature. 2018;559(7712):61-66.
Kamani NR, Kumar S, Hassebroek A, et al. Malignancies after hematopoietic cell transplantation for primary immune deficiencies: a report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2011;17(12):1783-1789.
Paronetto MP. Ewing sarcoma protein: a key player in human cancer. Int J Cell Biol. 2013;2013:642853.
Grünewald TGP, Cidre-Aranaz F, Surdez D, et al. Ewing sarcoma. Nat Rev Dis Primers. 2018;4(1):5.
Blevins MA, Huang M, Zhao R. The role of CtBP1 in oncogenic processes and its potential as a therapeutic target. Mol Cancer Ther. 2017;16(6):981-990.
Katsanis N, Fisher EM. A novel C-terminal binding protein (CTBP2) is closely related to CTBP1, an adenovirus E1A-binding protein, and maps to human chromosome 21q21.3. Genomics. 1998;47(2):294-299.
Calabrese C, Davidson NR, Demircioğlu D, et al. Genomic basis for RNA alterations in cancer. Nature. 2020;578(7793):129-136.
Shirakihara T, Horiguchi K, Miyazawa K, et al. TGF-β regulates isoform switching of FGF receptors and epithelial-mesenchymal transition. EMBO J. 2011;30(4):783-795.
Misiorek JO, Przybyszewska-Podstawka A, Kałafut J, et al. Context matters: NOTCH signatures and pathway in cancer progression and metastasis. Cells. 2021;10(1):94.
Oswald F, Winkler M, Cao Y, et al. RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes. Mol Cell Biol. 2005;25(23):10379-10390.
Katoh M, Nakagama H. FGF receptors: cancer biology and therapeutics. Med Res Rev. 2014;34(2):280-300.
Hardy KM, Yatskievych TA, Konieczka J, Bobbs AS, Antin PB. FGF signalling through RAS/MAPK and PI3K pathways regulates cell movement and gene expression in the chicken primitive streak without affecting E-cadherin expression. BMC Dev Biol. 2011;11:20.
Rash BG, Lim HD, Breunig JJ, Vaccarino FM. FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis. J Neurosci. 2011;31(43):15604-15617.
Small D, Kovalenko D, Soldi R, et al. Notch activation suppresses fibroblast growth factor-dependent cellular transformation. J Biol Chem. 2003;278(18):16405-16413.
Spans L, Fletcher CD, Antonescu CR, et al. Recurrent MALAT1-GLI1 oncogenic fusion and GLI1 up-regulation define a subset of plexiform fibromyxoma. J Pathol. 2016;239(3):335-343.
Zheng X, Song T, Dou C, Jia Y, Liu Q. CtBP2 is an independent prognostic marker that promotes GLI1 induced epithelial-mesenchymal transition in hepatocellular carcinoma. Oncotarget. 2015;6(6):3752-3769.