Individuals with short telomeres should be at increased risk for cancer, since short telomeres lead to genomic instability – a hallmark of cancer. However, individuals with long telomeres also display an increased risk for major cancers, thus creating a cancer-telomere length (TL) paradox. The two-stage clonal expansion model we propose is based on the thesis that a series of mutational hits (1st Hit) at the stem-cell level generates a clone with replicative advantage. A series of additional mutational hits (2nd Hit) transforms the expanding clone into cancer. By proposing that the 1st Hit is largely telomere length-independent, while the 2nd Hit is largely TL-dependent, we resolve the paradox, highlighting a regulatory role of telomeres in cancer.
|Original language||English (US)|
|Number of pages||6|
|Journal||Trends in Cancer|
|State||Published - Apr 2017|
All Science Journal Classification (ASJC) codes
- Cancer Research
- stem cells