The three-dimensional order of telomeres impacts on tumorigenesis

摘要: Proc Amer Assoc Cancer Res, Volume 47, 2006 4985 Telomeres of normal cells are organized in a non-overlapping manner the three-dimensional (3D) space interphase nucleus. In contrast, nuclei tumor display an aberrant organization telomeres: Telomeres from clusters, so called telomeric aggregates (TA)1. We have recently reported that c-Myc deregulation induces cycles TA formation and remodels nucleus by changing chromosomes 2. The conditional expression wild-type (wt) Myc deleted box II mutant-Myc (D106-myc) spontaneously immortalized mouse BaF3 pro-lymphocytes was previously characterized 3. Mutant protein induced lower level apoptosis but higher genomic instability than its wt counterpart this model, tumorigenesis two separable events because only wt-myc not D106-myc expressing SCID model 4. Here we investigated possible correlation between formation, telomere localization cells. PNA-FISH hybridization 3D-fixed showed did induce TAs. aligned center 3D forming new structure disk. This telomeres is related to arrest cell cycle G0/G1 after expression. first time such found at G1/S block. block confirmed FACS analysis conditions normally arrest. G1-S transition caused distorted distribution. Analysis chromosomal alteration using spectral karyotyping (SKY) high levels Myc-associated instability. A significant number fusions were noted study confirms fundamental role Myc-induced provides novel way dissect initiation. 1 Chuang et al., BMC Biol. 2(1):12, 2004 2 Louis Natl Acad Sci U S A. 102(27):9613-8, 2005 3 Fest Oncogene 21(19):2981-90, 2002 4 24(18):2944-53,