Mutations, Cancer and the Telomere Length Paradox

Abraham Aviv, James J. Anderson, Jerry W. Shay

Research output: Contribution to journalReview articlepeer-review

79 Scopus citations


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 languageEnglish (US)
Pages (from-to)253-258
Number of pages6
JournalTrends in Cancer
Issue number4
StatePublished - Apr 2017


  • cancer
  • clones
  • evolution
  • mutation
  • stem cells
  • telomeres

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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