GREB1-CTNNB1 fusion transcript detected by RNA-sequencing in a uterine tumor resembling ovarian sex cord tumor (UTROSCT): a novel CTNNB1 rearrangement.
Fiche publication
Date publication
octobre 2018
Journal
Genes, chromosomes & cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ARNOULD Laurent, Dr AVEROUS Gerlinde
Tous les auteurs :
Croce S, Lesluyes T, Delespaul L, Bonhomme B, Pérot G, Velasco V, Mayeur L, Rebier F, Ben Rejeb H, Guyon F, McCluggage WG, Floquet A, Querleu D, Chakiba C, Devouassoux-Shisheboran M, Mery E, Arnould L, Averous G, Soubeyran I, Le Guellec S, Chibon F
Lien Pubmed
Résumé
Mutations in the phosphorylation sites in exon 3 of CTNNB1 have been implicated in tumorigenesis in many organs. However, tumors harboring a CTNNB1 translocation are extremely rare and CTNNB1 translocation has never been reported in a uterine mesenchymal neoplasm. We report a novel translocation t(2;3)(p25;p22) involving the GREB1 (intron 8) and CTNNB1 (exon 3) genes in a uterine tumor resembling ovarian sex cord tumor (UTROSCT) which exhibited early extrauterine metastasis. The translocation was detected by RNA-sequencing and validated by RT-PCR and resulted in nuclear expression of β-catenin. The resulting chimeric transcript had a stop codon for GREB1 (intron 8) and a new start codon for CTNNB1 (exon 4). Juxtapositioning with GREB1, which is overexpressed in response to estrogens, resulted in overexpression of a truncated and hypophosphorylated nuclear β-catenin in the primary and recurrent tumors. This accumulation of nuclear β-catenin results in a constitutive activation of the Wnt/β-catenin signaling pathway with a major oncogenic effect. The CTNNB1 gene fusion, promoted by an estrogen-responsive gene (GREB1), could be a potential driver of tumorigenesis in this case and a possible therapeutic target with adapted inhibitors. RT-PCR and immunohistochemistry performed on 11 additional UTROSCTs showed no CTNNB1 fusion transcript or nuclear β-catenin immunoreactivity. This article is protected by copyright. All rights reserved.
Mots clés
UTROSCT, cytogenetic, molecular biology, pathology, translocation
Référence
Genes Chromosomes Cancer. 2018 Oct 23;: