Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Cancer chromosomes going to POT1

Nature Genetics volume 45, pages 473–475 (2013)Cite this article

Subjects

Alterations in the single-stranded telomere–binding protein POT1 have recently been identified in chronic lymphocytic leukemia. This discovery provides novel insights into how genomic instability induced by dysfunctional telomeres contributes to tumorigenesis.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, with an estimated incidence of 3.9 cases per 100,000 people in the United States and a median age of 72 years at the time of diagnosis1. CLL is clinically heterogeneous, with variable presentations and patient outcomes. Whereas it is indolent in many patients, in others it is highly aggressive, resulting in rapid mortality. This clinical variability is likely due to the fact that CLL is genetically heterogeneous. Recent next-generation whole-genome and exome sequencing approaches have shown that CLLs possess strikingly complex genomic profiles, highlighted by multiple aberrations in chromosome structure and pathogenic mutations in at least seven distinct genetic pathways2,3,4. On page 526 of this issue, Carlos López-Otín and colleagues implicate telomere end protection as yet another genetic pathway perturbed in CLL5. They found that somatic mutations in the POT1 gene (encoding protection of telomere 1) are present in 3.5% of all CLL cases, occurring exclusively in the clinically aggressive CLL subtype with wild-type IGHV@. When they ranked CLL mutations by corrected frequency scores, which take into account gene size, the number of mutations found in the gene and codon composition, POT1 emerged as the second most frequently mutated gene. Clonal and subclonal analyses showed that POT1 mutations arise early, suggesting that they likely represent driver mutations in CLL4. POT1 is the first component of the telomere shelterin complex found to be mutated in human cancer, and this discovery further supports the hypothesis that telomere dysfunction results in the genomic rearrangements that are permissive for cancer initiation and progression6.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: POT1 mutations in CLL promote chromosomal aberrations and telomere extension.

References

  1. Zenz, T., Mertens, D., Kuppers, R., Dohner, H. & Stilgenbauer, S. Nat. Rev. Cancer 10, 37–50 (2010).

    Article  CAS  Google Scholar 

  2. Puente, X.S. et al. Nature 475, 101–105 (2011).

    Article  CAS  Google Scholar 

  3. Wang, L. et al. N. Engl. J. Med. 365, 2497–2506 (2011).

    Article  CAS  Google Scholar 

  4. Landau, D.A. et al. Cell 152, 714–726 (2013).

    Article  CAS  Google Scholar 

  5. Ramsay, A.J. et al. Nat. Genet. 45, 526–530 (2013).

    Article  CAS  Google Scholar 

  6. Maser, R.S. & DePinho, R.A. Science 297, 565–569 (2002).

    Article  CAS  Google Scholar 

  7. Palm, W. & de Lange, T. Annu. Rev. Genet. 42, 301–334 (2008).

    Article  CAS  Google Scholar 

  8. Wu, L. et al. Cell 126, 49–62 (2006).

    Article  CAS  Google Scholar 

  9. Hockemeyer, D., Daniels, J.P., Takai, H. & de Lange, T. Cell 126, 63–77 (2006).

    Article  CAS  Google Scholar 

  10. Lam, Y.C. et al. EMBO J. 29, 2230–2241 (2010).

    Article  CAS  Google Scholar 

  11. Sfeir, A., Kabir, S., van Overbeek, M., Celli, G.B. & de Lange, T. Science 327, 1657–1661 (2010).

    Article  CAS  Google Scholar 

  12. Flynn, R.L. et al. Nature 471, 532–536 (2011).

    Article  CAS  Google Scholar 

  13. Xin, H. et al. Nature 445, 559–562 (2007).

    Article  CAS  Google Scholar 

  14. Wang, F. et al. Nature 445, 506–510 (2007).

    Article  CAS  Google Scholar 

  15. Lin, T.T. et al. Blood 116, 1899–1907 (2010).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sandy Chang is in the Department of Laboratory Medicine and Pathology at Yale University School of Medicine, New Haven, Connecticut, USA.,

    Sandy Chang

Authors
  1. Sandy Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sandy Chang.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chang, S. Cancer chromosomes going to POT1. Nat Genet 45, 473–475 (2013). https://doi.org/10.1038/ng.2617

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.2617

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer