Fiche publication
Date publication
novembre 2014
Journal
The American journal of pathology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BENSUSSAN Armand
Tous les auteurs :
Sako N, Dessirier V, Bagot M, Bensussan A, Schmitt C
Lien Pubmed
Résumé
Extranodal natural killer-T-cell lymphoma (NKTCL) of nasal type is a malignant disorder of cytotoxic lymphocytes of natural killer or more rarely T cells, associated with clonal Epstein-Barr virus infection. NKTCL is an aggressive neoplasm with very poor prognosis. Although the pathogenesis of NKTCL is little understood, some insight has been gained in the recent years, especially from genome-wide studies, which revealed a deletion on chromosome 6q21 in more than 50% of patients. Of interest, this deleted region contains four candidate tumor suppressor genes whose decreased expression has been confirmed at the mRNA level: PRDM1, ATG5, AIM1, and HACE1. Mutations and methylation in PRDM1, ATG5, and AIM1 have been reported in NKTCL cell lines. We investigated the involvement of HACE1 in NKTCL pathophysiology. Even though the hypermethylation of CpG-177 island located directly upstream of HACE1 locus led to down-regulation of HACE1 mRNA, the protein product was expressed at nearly normal levels and was functional in the NKTCL cell lines regardless of 6q21 deletion (and indeed no double deletion of 6q21 and no nonfunctional mutations have been reported). Furthermore, contrary to previous report, overexpression of HACE1 by transduction of recombinant protein did not affect proliferation or survival of NKTCL cell lines. We therefore conclude that HACE1 is not directly involved in NKTCL pathophysiology.
Mots clés
Apoptosis, genetics, Cell Cycle, genetics, Cell Proliferation, genetics, CpG Islands, DNA Methylation, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Lymphoma, Extranodal NK-T-Cell, genetics, Ubiquitin-Protein Ligases, genetics
Référence
Am J Pathol. 2014 11;184(11):2899-907
