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.

GERMLINE MUTATIONS

How the germline informs the somatic landscape

Nature Genetics volume 53, pages 1523–1525 (2021)Cite this article

Subjects

How somatic and germline mutations interact in cancer remains largely unexplored. A study of 17,152 patients with cancer suggests that the relative contribution of pathogenic germline mutations is governed by lineage and penetrance.

In 1866, the neuroscientist Paul de Broca noted the clustering of breast cancer cases within his wife’s extended family, and suggested that it was more than a coincidence1. Over the next century and a half, cancer researchers have pursued parallel efforts that address the importance of both germline and somatic events, generating insights into the processes that underpin cancer development. This has led us to a key inflection point, as each cancer is complex and unique, yet there are common threads that determine basic mechanisms that can guide therapeutic decisions and even prevention. Comprehensive characterization with new ‘omic’ tools has produced landscape snapshots of somatic alterations in distinct cancers. The catalog of known cancer driver genes has led to an explosion in efforts to understand how a cancer sustains itself, once initiated, presumably by germline or somatic driver mutations2. Somatic landscape analyses have facilitated investigations into the devolution of a tumor, constructing genetic maps using passenger mutations, to investigate how individual cancers arose owing to intrinsic errors and external exposures3.

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

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Dynamic model of carcinogenesis.

References

  1. Broca P. Traité de Tumeurs (P. Asselin, 1866).

  2. Sondka, Z. et al. Nat. Rev. Cancer 18, 696–705 (2018).

    Article  CAS  Google Scholar 

  3. Alexandrov, L. B. et al. Nature 500, 415–421 (2013).

    Article  CAS  Google Scholar 

  4. Knudson, A. G. Proc. Natl Acad. Sci. USA 68, 820–823 (1971).

    Article  Google Scholar 

  5. Rahman, N. Nature 505, 302–308 (2014).

    Article  CAS  Google Scholar 

  6. Park, S. L. et al. Cancer Epidemiol. Biomarkers Prev. 27, 405–417 (2018).

    Article  CAS  Google Scholar 

  7. Srinivasan, P. et al. Nat. Genet. https://doi.org/10.1038/s41588-021-00949-1 (2021).

  8. Huang, K.-l et al. Cell 173, 355–370 (2018).

    Article  CAS  Google Scholar 

  9. Tavtigian, S. et al. Hum. Mutat. 29, 1261–1264 (2008).

    Article  CAS  Google Scholar 

  10. De Andrade, K. et al. Hum. Mutat. 40, 97–105 (2019).

    Article  Google Scholar 

  11. Moore, L. et al. Nature 597, 381–386 (2021).

    Article  CAS  Google Scholar 

  12. Wilkinson, M. D. et al. Sci. Data 6, 174 (2016).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Stephen J. Chanock

Authors
  1. Stephen J. Chanock
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen J. Chanock.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chanock, S.J. How the germline informs the somatic landscape. Nat Genet 53, 1523–1525 (2021). https://doi.org/10.1038/s41588-021-00960-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41588-021-00960-6

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