fr
Article scientifique
Anglais

Ataxia-telangiectasia mutated (ATM) silencing promotes neuroblastoma progression through a MYCN independent mechanism

Publié dansOncotarget, vol. 6, no. 21, p. 18558-18576
Date de publication2015
Résumé

Neuroblastoma, a childhood cancer with highly heterogeneous biology and clinical behavior, is characterized by genomic aberrations including amplification of MYCN. Hemizygous deletion of chromosome 11q is a well-established, independent marker of poor prognosis. While 11q22-q23 is the most frequently deleted region, the neuroblastoma tumor suppressor in this region remains to be identified. Chromosome bands 11q22-q23 contain ATM, a cell cycle checkpoint kinase and tumor suppressor playing a pivotal role in the DNA damage response. Here, we report that haploinsufficiency of ATM in neuroblastoma correlates with lower ATM expression, event-free survival, and overall survival. ATM loss occurs in high stage neuroblastoma without MYCN amplification. In SK-N-SH, CLB-Ga and GI-ME-N human neuroblastoma cells, stable ATM silencing promotes neuroblastoma progression in soft agar assays, and in subcutaneous xenografts in nude mice. This effect is dependent on the extent of ATM silencing and does not appear to involve MYCN. Our findings identify ATM as a potential haploinsufficient neuroblastoma tumor suppressor, whose inactivation mirrors the increased aggressiveness associated with 11q deletion in neuroblastoma.

Citation (format ISO)
MANDRIOTA, Stefano J et al. Ataxia-telangiectasia mutated (ATM) silencing promotes neuroblastoma progression through a MYCN independent mechanism. In: Oncotarget, 2015, vol. 6, n° 21, p. 18558–18576. doi: 10.18632/oncotarget.4061
Fichiers principaux (1)
Article (Published version)
accessLevelRestricted
Identifiants
ISSN du journal1949-2553
461vues
0téléchargements

Informations techniques

Création08/09/2015 12:11:00
Première validation08/09/2015 12:11:00
Heure de mise à jour14/03/2023 23:42:16
Changement de statut14/03/2023 23:42:16
Dernière indexation16/01/2024 19:10:07
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack