期刊
CELL REPORTS
卷 19, 期 12, 页码 2544-2556出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.05.087
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资金
- National Health and Medical Research Council of Australia (NHMRC) [1051898]
- Cancer Council New South Wales (NSW) [PG11-08]
- NHMRC Early Career Fellowship [1012500]
- Pablove Foundation
- Cancer Institute NSW (CINSW) [15/CD/1-08, 12/CDF/2-26]
- Harry Banks Sutherland Rotary PhD Scholarship
- Kids Cancer Alliance/CINSW
- Cancer Prevention and Research Institute of Texas [RP170510]
Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative. Here, we show that a subset of high-risk neuroblastomas (with similar to 50% 5-year mortality) lacked significant TLM activity. Cancer cells derived from these highly aggressive tumors initially had long telomeres and proliferated for > 200 population doublings with ever-shorter telomeres. This indicates that prevention of telomere shortening is not always required for oncogenesis, which has implications for inhibiting TLMs for cancer therapy.
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