Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Science. 2011 Jul 22;333(6041):425. doi: 10.1126/science.1207313. Epub 2011 Jun 30.
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.
ATR 和 DAXX 编码的蛋白参与端粒和其他基因组位点的染色质重塑。因为这些基因的失活突变在人类胰腺神经内分泌肿瘤（PanNETs）中很常见，我们检查了这些肿瘤的端粒状态。我们发现，61%的 PanNETs 显示出异常的端粒，这些端粒具有端粒酶独立的端粒维持机制的特征，称为 ALT（端粒的替代性延长）。所有表现出这些异常端粒的 PanNETs 都有 ATRX 或 DAXX 突变或核 ATRX 或 DAXX 蛋白缺失。ATR 突变也与中枢神经系统肿瘤中的异常端粒相关。这些数据表明，在 ATR 或 DAXX 基因改变的人类肿瘤中，可能存在替代性端粒维持功能。
