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Altered Telomeres in Tumors with ATRX and DAXX Mutations

2011; American Association for the Advancement of Science; Volume: 333; Issue: 6041 Linguagem: Inglês

10.1126/science.1207313

1095-9203

Christopher M. Heaphy, Roeland F. de Wilde, Yuchen Jiao, Alison P. Klein, Barish H. Edil, Chanjuan Shi, Chetan Bettegowda, Fausto J. Rodríguez, Charles G. Eberhart, Sachidanand Hebbar, G. Johan A. Offerhaus, Roger E. McLendon, B. Ahmed Rasheed, Yiping He, Hai Yan, Darell D. Bigner, Sueli Mieko Oba‐Shinjo, Suely Kazue Nagahashi Marie, Gregory J. Riggins, Kenneth W. Kinzler, Bert Vogelstein, Ralph H. Hruban, Anirban Maitra, Nickolas Papadopoulos, Alan K. Meeker,

Advanced biosensing and bioanalysis techniques

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.