title: Altered telomeres in tumors with ATRX and DAXX mutations.
abstract: The proteins encoded by ATRX and DAXX participate in chromatin remodeling at telomeres and other genomic sites. Because inactivating mutations of these genes are common in human pancreatic neuroendocrine tumors (PanNETs), we examined the telomere status of these tumors. We found that 61% of PanNETs displayed abnormal telomeres that are characteristic of a telomerase-independent telomere maintenance mechanism termed ALT (alternative lengthening of telomeres). All of the PanNETs exhibiting these abnormal telomeres had ATRX or DAXX mutations or loss of nuclear ATRX or DAXX protein. ATRX mutations also correlate with abnormal telomeres in tumors of the central nervous system. These data suggest that an alternative telomere maintenance function may operate in human tumors with alterations in the ATRX or DAXX genes.
authors: Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors: Christopher M
authors: CM
authors: Heaphy
authors: Roeland F
authors: RF
authors: de Wilde
authors: Yuchen
authors: Y
authors: Jiao
authors: Alison P
authors: AP
authors: Klein
authors: Barish H
authors: BH
authors: Edil
authors: Chanjuan
authors: C
authors: Shi
authors: Chetan
authors: C
authors: Bettegowda
authors: Fausto J
authors: FJ
authors: Rodriguez
authors: Charles G
authors: CG
authors: Eberhart
authors: Sachidanand
authors: S
authors: Hebbar
authors: G Johan
authors: GJ
authors: Offerhaus
authors: Roger
authors: R
authors: McLendon
authors: B Ahmed
authors: BA
authors: Rasheed
authors: Yiping
authors: Y
authors: He
authors: Hai
authors: H
authors: Yan
authors: Darell D
authors: DD
authors: Bigner
authors: Sueli Mieko
authors: SM
authors: Oba-Shinjo
authors: Suely Kazue Nagahashi
authors: SK
authors: Marie
authors: Gregory J
authors: GJ
authors: Riggins
authors: Kenneth W
authors: KW
authors: Kinzler
authors: Bert
authors: B
authors: Vogelstein
authors: Ralph H
authors: RH
authors: Hruban
authors: Anirban
authors: A
authors: Maitra
authors: Nickolas
authors: N
authors: Papadopoulos
authors: Alan K
authors: AK
authors: Meeker
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D018278:Carcinoma, Neuroendocrine / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002467:Cell Nucleus / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D042002:Chromatin Assembly and Disassembly; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018832:Molecular Chaperones; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D016615:Telomere / Q000502:physiology* / Q000648:ultrastructure; D000075924:X-linked Nuclear Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D050505:Mutant Proteins; D009687:Nuclear Proteins; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein