Long telomeres and cancer risk: the price of cellular immortality
Emily J. McNally,1,2 Paz J. Luncsford,1,2 and Mary Armanios1,2,3,4
1Department of Oncology,
2Telomere Center,
3Sidney Kimmel Comprehensive Cancer Center, and
4McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Address correspondence to: Mary Armanios, 1650 Orleans Street, CRB 1 Room 186, Baltimore, Maryland 21287, USA. Phone: 410.502.2817; Email: marmani1@jhmi.edu.
Find articles by McNally, E. in: JCI | PubMed | Google Scholar
1Department of Oncology,
2Telomere Center,
3Sidney Kimmel Comprehensive Cancer Center, and
4McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Address correspondence to: Mary Armanios, 1650 Orleans Street, CRB 1 Room 186, Baltimore, Maryland 21287, USA. Phone: 410.502.2817; Email: marmani1@jhmi.edu.
Find articles by Luncsford, P. in: JCI | PubMed | Google Scholar
1Department of Oncology,
2Telomere Center,
3Sidney Kimmel Comprehensive Cancer Center, and
4McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Address correspondence to: Mary Armanios, 1650 Orleans Street, CRB 1 Room 186, Baltimore, Maryland 21287, USA. Phone: 410.502.2817; Email: marmani1@jhmi.edu.
Find articles by Armanios, M. in: JCI | PubMed | Google Scholar
First published August 5, 2019 - More info
J Clin Invest. 2019;129(9):3474–3481. https://doi.org/10.1172/JCI120851.
© 2019 American Society for Clinical Investigation
The distribution of telomere length in humans is broad, but it has finite upper and lower boundaries. Growing evidence shows that there are disease processes that are caused by both short and long telomere length extremes. The genetic basis of these short and long telomere syndromes may be linked to mutations in the same genes, such as the telomerase reverse transcriptase (TERT), but through differential effects on telomere length. Short telomere syndromes have a predominant degenerative phenotype marked by organ failure that most commonly manifests as pulmonary fibrosis and are associated with a relatively low cancer incidence. In contrast, insights from studies of cancer-prone families as well as genome-wide association studies (GWAS) have identified both rare and common variants that lengthen telomeres as being strongly associated with cancer risk. We have hypothesized that these cancers represent a long telomere syndrome that is associated with a high penetrance of cutaneous melanoma and chronic lymphocytic leukemia. In this Review, we will synthesize the clinical and human genetic observations with data from mouse models to define the role of telomeres in cancer etiology and biology.
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Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)