Title: Gene expression signatures identify rhabdomyosarcoma subtypes and detect a novel t(2;2)(q35;p23) translocation fusing PAX3 to NCOA1
Authors : Wachtel, Marco
Dettling, Marcel
Koscielniak, Eva
Stegmaier, Sabine
Treuner, Jörn
Simon-Klingenstein, Katja
Bühlmann, Peter
Niggli, Felix K.
Schäfer, Beat W.
Published in : Cancer Research
Volume(Issue) : 64
Issue : 16
Pages : 5539
Pages to: 5545
Publisher / Ed. Institution : American Association for Cancer Research
Publisher / Ed. Institution: Philadelphia
Issue Date: 2004
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (Publication)
Language : English
Subjects : Base sequence; Chromosomes, human, pair 2; DNA-binding proteins; Gene expression profiling; Histone acetyltransferases; Humans; Molecular sequence data; Nuclear receptor coactivator 1; Oligonucleotide array sequence analysis; Oncogene proteins, fusion; PAX3 transcription factor; Paired box transcription factors; Rhabdomyosarcoma, alveolar; Rhabdomyosarcoma, embryonal; Trans-activators; Transcription factors; Translocation, genetic
Subject (DDC) : 572: Biochemistry
Abstract: Rhabdomyosarcoma is a pediatric tumor type, which is classified based on histological criteria into two major subgroups, namely embryonal rhabdomyosarcoma and alveolar rhabdomyosarcoma. The majority, but not all, alveolar rhabdomyosarcoma carry the specific PAX3(7)/FKHR-translocation, whereas there is no consistent genetic abnormality recognized in embryonal rhabdomyosarcoma. To gain additional insight into the genetic characteristics of these subtypes, we used oligonucleotide microarrays to measure the expression profiles of a group of 29 rhabdomyosarcoma biopsy samples (15 embryonal rhabdomyosarcoma, and 10 translocation-positive and 4 translocation-negative alveolar rhabdomyosarcoma). Hierarchical clustering revealed expression signatures clearly discriminating all three of the subgroups. Differentially expressed genes included several tyrosine kinases and G protein-coupled receptors, which might be amenable to pharmacological intervention. In addition, the alveolar rhabdomyosarcoma signature was used to classify an additional alveolar rhabdomyosarcoma case lacking any known PAX3 or PAX7 fusion as belonging to the translocation-positive group, leading to the identification of a novel translocation t(2;2)(q35;p23), which generates a fusion protein composed of PAX3 and the nuclear receptor coactivator NCOA1, having similar transactivation properties as PAX3/FKHR. These experiments demonstrate for the first time that gene expression profiling is capable of identifying novel chromosomal translocations.
Departement: School of Engineering
Publication type: Article in scientific Journal
DOI : 10.1158/0008-5472.CAN-04-0844
ISSN: 0008-5472
URI: https://digitalcollection.zhaw.ch/handle/11475/4637
Appears in Collections:Publikationen School of Engineering

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