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.

  • Comment
  • Published:

Towards the understanding of the genetics of somatic mutations

British Journal of Cancer volume 125, pages 627–628 (2021)Cite this article

Subjects

Summary

A recent study from Sun et al. reveals a polygenic architecture for pan-cancer tumour mutational burden (TMB) and shows the identification of genes underpinning the associations between germline genetic variants and TMB in specific cancer types. Here we discuss the main findings of the Sun et al. study and the implications for further studies.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

References

  1. Hellmann, M. D., Ciuleanu, T. E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C. et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N. Engl. J. Med. 378, 2093–2104 (2018).

    Article  CAS  Google Scholar 

  2. Samstein, R. M., Lee, C. H., Shoushtari, A. N., Hellmann, M. D., Shen, R., Janjigian, Y. Y. et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat. Genet. 51, 202–206 (2019).

    Article  CAS  Google Scholar 

  3. Sun, X., Xue, A., Qi, T., Chen, D., Shi, D., Wu, Y. et al. Tumor mutational burden is polygenic and genetically associated with complex traits and diseases. Cancer Res. 81, 1230–1239 (2021).

    Article  CAS  Google Scholar 

  4. Zeng, J., de Vlaming, R., Wu, Y., Robinson, M. R., Lloyd-Jones, L. R., Yengo, L. et al. Signatures of negative selection in the genetic architecture of human complex traits. Nat. Genet. 50, 746–753 (2018).

    Article  CAS  Google Scholar 

  5. Carrot-Zhang, J., Soca-Chafre, G., Patterson, N., Thorner, A. R., Nag, A., Watson, J. et al. Genetic ancestry contributes to somatic mutations in lung cancers from admixed Latin American populations. Cancer Discov. 11, 591–598 (2021).

    Article  CAS  Google Scholar 

  6. Chen, J., Yang, H., Teo, A. S. M., Amer, L. B., Sherbaf, F. G., Tan, C. Q. et al. Genomic landscape of lung adenocarcinoma in East Asians. Nat. Genet. 52, 177–186 (2020).

    Article  CAS  Google Scholar 

  7. Moamer, A., Hachim, I. Y., Binothman, N., Wang, N., Lebrun, J. J. & Ali, S. A role for kinesin-1 subunits KIF5B/KLC1 in regulating epithelial mesenchymal plasticity in breast tumorigenesis. EBioMedicine 45, 92–107 (2019).

    Article  Google Scholar 

  8. Alexandrov, L. B., Ju, Y. S., Haase, K., Van Loo, P., Martincorena, I., Nik-Zainal, S. et al. Mutational signatures associated with tobacco smoking in human cancer. Science 354, 618–622 (2016).

    Article  CAS  Google Scholar 

  9. Kucab, J. E., Zou, X., Morganella, S., Joel, M., Nanda, A. S., Nagy, E. et al. A compendium of mutational signatures of environmental agents. Cell 177, 821–836 e816 (2019).

    Article  CAS  Google Scholar 

  10. Yoshida, K., Gowers, K. H. C., Lee-Six, H., Chandrasekharan, D. P., Coorens, T., Maughan, E. F. et al. Tobacco smoking and somatic mutations in human bronchial epithelium. Nature 578, 266–272 (2020).

    Article  CAS  Google Scholar 

  11. Gandara, D. R., Paul, S. M., Kowanetz, M., Schleifman, E., Zou, W., Li, Y. et al. Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nat. Med. 24, 1441–1448 (2018).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Not applicable.

Author information

Authors and Affiliations

  1. Institute for Advanced Research, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Xiwei Sun

  2. School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China

    Xiwei Sun & Jian Yang

  3. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China

    Jian Yang

Authors
  1. Xiwei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

X.S. and J.Y. wrote the manuscript.

Corresponding author

Correspondence to Jian Yang.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Data availability

Not applicable.

Competing interests

The authors declare no competing interests.

Funding information

This work is partly supported by the Westlake Education Foundation.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, X., Yang, J. Towards the understanding of the genetics of somatic mutations. Br J Cancer 125, 627–628 (2021). https://doi.org/10.1038/s41416-021-01369-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-021-01369-y

Search

Advanced search

Quick links