title: OTX2 Defines a Subgroup of Atypical Teratoid Rhabdoid Tumors With Close Relationship to Choroid Plexus Tumors.
abstract: Atypical teratoid rhabdoid tumors (ATRT) are highly malignant brain tumors of early childhood that have been regarded as a homogenous entity characterized by inactivation of the SMARCB1/INI1 or SMARCA4/BRG1 genes as the only characteristic alteration. Recent studies suggest that similar to other embryonal tumors ATRT can also be divided into subgroups based on their mRNA or methylation profiles. Using microarray-based expression analysis of 12 patient ATRT specimens we demonstrated the existence of 2 subgroups of ATRT. One subgroup is characterized by high expression of OTX2, encoding a transcription factor involved in brain development. OTX2 expression was verified by immunohistochemistry and might function as a novel therapeutic target for this fatal tumor. High expression of OTX2 as well as expression of Kir7.1/KCNJ13, TRPM3 and ENPP2, which have all previously been linked to either choroid plexus epithelium or choroid plexus tumors (CPTs), suggests a close histogenetic relation of this subgroup to CPTs.
authors.affiliation: Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Anna Sophia
authors.initials: AS
authors.lastname: Japp
authors.affiliation: Department of Cell Biology (Tumor Research), University of Duisburg-Essen, Essen, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.affiliation: Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Dorota
authors.initials: D
authors.lastname: Denkhaus
authors.affiliation: Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D016545:Choroid Plexus Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051857:Otx Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D018335:Rhabdoid Tumor / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D013724:Teratoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C497659:OTX2 protein, human; D051857:Otx Transcription Factors
keywords: Atypical teratoid rhabdoid tumors; Choroid plexus tumors; Gene expression analysis; MITF; OTX2; SMARCB1/INI1