title: Identification by FFPE RNA-Seq of a new recurrent inversion leading to RBM10-TFE3 fusion in renal cell carcinoma with subtle TFE3 break-apart FISH pattern.
abstract: Gene fusions involving TFE3 defines the "Xp11.2 translocations" subclass of renal cell carcinomas (RCCs) belonging to the MiT family translocation RCC. Four recurrent TFE3 fusion partners were identified to date: PRCC, ASPSCR1, SFPQ, and NONO. Break-apart TFE3 fluorescence in situ hybridization (FISH) on formalin-fixed and paraffin-embedded (FFPE) tissue sections is currently the gold standard for identification of TFE3 rearrangements. Herein, we report a case of RCC with a morphological appearance of Xp11.2 translocation, and positive TFE3 immunostaining. By FISH, the spots constituting the split signal were barely spaced, suggestive of a chromosome X inversion rather than a translocation. We performed RNA-seq from FFPE material to test this hypothesis. RNA-seq suggested a fusion of RBM10 gene exon 17 (Xp11.23) with TFE3 gene exon 5 (Xp11.2). RBM10-TFE3 fusion transcript was confirmed using specific RT-PCR. Our work showed that RNA-Seq is a robust technique to detect fusion transcripts from FFPE material. A RBM10-TFE3 fusion was previously described in single case of Xp11.2 RCC. Although rare, RBM10-TFE3 fusion variant (from chromosome X paracentric inversion), therefore, appears to be a recurrent molecular event in Xp11.2 RCCs. RBM10-TFE3 fusion should be added in the list of screened fusion transcripts in targeted molecular diagnostic multiplex RT-PCR. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Pathology Department, AP-HP, Hôpitaux universitaires Paris-Centre, Hôpital Cochin; Faculté de médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|INSERM, U1016, Institut Cochin, and CNRS, UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Just
authors.affiliation: Plateforme Génomique, Institut Cochin, CNRS UMR_S1016, INSERM U1016, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Letourneur
authors.affiliation: Pathology Department, AP-HP, Hôpitaux universitaires Paris-Centre, Hôpital Cochin; Faculté de médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Pouliquen
authors.affiliation: Service d'anatomopathologie, CHC, Clinique Saint-Joseph, Université de Liège, Liège, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Dome
authors.affiliation: Pathology Department, AP-HP, Hôpitaux universitaires Paris-Centre, Hôpital Cochin; Faculté de médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Audebourg
authors.affiliation: Service d'Urologie, CHC, Clinique Saint-Joseph, Université de Liège, Liège, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Biquet
authors.affiliation: Department of Molecular Genetics, AP-HP, Hôpitaux universitaires Paris-Centre, Hôpital Cochin, Paris, France.|EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Vidaud
authors.affiliation: Pathology Department, AP-HP, Hôpitaux universitaires Paris-Centre, Hôpital Cochin; Faculté de médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|INSERM, U1016, Institut Cochin, and CNRS, UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Terris
authors.affiliation: Pathology Department, AP-HP, Hôpitaux universitaires Paris-Centre, Hôpital Cochin; Faculté de médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|INSERM, U1016, Institut Cochin, and CNRS, UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Sibony
authors.affiliation: Department of Molecular Genetics, AP-HP, Hôpitaux universitaires Paris-Centre, Hôpital Cochin, Paris, France.|EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Pasmant
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D041321:Chromosomes, Human, X; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016612:Paraffin Embedding; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015514:Oncogene Proteins, Fusion; C512260:RBM10 protein, human; D016601:RNA-Binding Proteins; C069203:TFE3 protein, human