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Johnson JE , Gettings EJ , Schwalm J , Pei JM , Testa JR , Litwin S , von Mehren M , Broccoli D
Whole-genome profiling in liposarcomas reveals genetic alterations common to specific telomere maintenance mechanisms
Cancer Research. 2007 Oct;67(19) :9221-9228
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Telomere attrition ultimately leads to the activation of protective cellular responses, such as apoptosis or senescence. Impairment of such mechanisms can allow continued proliferation despite the presence of dysfunctional telomeres. Under such conditions, high levels of genome instability are often engendered. Data from both mouse and human model systems indicate that a period of genome instability might facilitate tumorigenesis. Here, we use a liposarcoma model system to assay telomere maintenance mechanism (TMM)-specific genetic alterations. A multiassay approach was used to assess the TMMs active in tumors. Genomic DNA from these samples was then analyzed by high-resolution DNA mapping array to identify genetic alterations. Our data reveal a higher level of genome instability in alternative lengthening of telomere (ALT)-positive tumors compared with telomerase-positive tumors, whereas tumors lacking both mechanisms have relatively low levels of genome instability. The!
ISI Document Delivery No.: 217NV Johnson, Jay E. Gettings, Edward J. Schwalm, Jaclyn Pei, Jianming Testa, Joseph R. Litwin, Samuel von Mehren, Margaret Broccoli, Dominique