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.

  • Correspondence
  • Published:

Pedigree analysis of a POLD1 germline mutation in urothelial carcinoma shows a close association between different mutation burdens and overall survival

Cellular & Molecular Immunology volume 18, pages 767–769 (2021)Cite this article

Subjects

Bladder cancer (BCa) is the ninth most frequently diagnosed tumor worldwide, and smoking remains a major risk factor. BCa is divided into nonmuscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).1 NMIBC accounts for 70–80% of all BCa cases, its recurrence rate is high, and 20–30% of NMIBC patients progress to MIBC.2

Over the last decade, the rise of next-generation sequencing (NGS), the coordinated efforts of The Cancer Genome Atlas (TCGA) program, and the breakthrough in basic research on cancer immunology have all promoted research on cancer mechanisms and novel treatment methods.3 These techniques and research have also contributed to the rise of tumor immunotherapy and the development of immune checkpoint inhibitors (such as programmed cell death protein 1 [PD-1], PD-1 ligand [PD-L1], and cytotoxic T-lymphocyte antigen-4 [CTLA-4]).

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

Relevant articles

Open Access articles citing this article.

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

Fig. 1

Data availability

All of the data from the analysis of the pedigree were included in our paper. The TCGA data can be downloaded from http://xena.ucsc.edu/. The COSMIC data can be downloaded from https://cancer.sanger.ac.uk/cosmic/download.

References

  1. Humphrey, P. A., Moch, H., Cubilla, A. L., Ulbright, T. M. & Reuter, V. E. The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: prostate and bladder tumours. Eur. Urol. 70, 106–119 (2016).

    Article  Google Scholar 

  2. Chamie, K. et al. Recurrence of high-risk bladder cancer: a population-based analysis. Cancer 119, 3219–3227 (2013).

    Article  Google Scholar 

  3. Charoentong, P. et al. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep. 18, 248–262 (2017).

    Article  CAS  Google Scholar 

  4. Palles, C. et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat. Genet. 45, 136–144 (2013).

    Article  CAS  Google Scholar 

  5. Cancer Genome Atlas Research Network Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507, 315–322 (2014).

    Article  Google Scholar 

  6. Knowles, M. A. & Hurst, C. D. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat. Rev. Cancer 15, 25–41 (2015).

    Article  CAS  Google Scholar 

  7. Mucci, L. A. et al. Familial risk and heritability of cancer among twins in Nordic countries. JAMA 315, 68–76 (2016).

    Article  CAS  Google Scholar 

  8. Nicolas, E., Golemis, E. A. & Arora, S. POLD1: central mediator of DNA replication and repair, and implication in cancer and other pathologies. Gene 590, 128–141 (2016).

    Article  CAS  Google Scholar 

  9. Briggs, S. & Tomlinson, I. Germline and somatic polymerase epsilon and delta mutations define a new class of hypermutated colorectal and endometrial cancers. J. Pathol. 230, 148–153 (2013).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the patients and their family members for participating in our study. We gratefully acknowledge the excellent technical assistance provided by Ms Yuan Zhu, Ms Shanshan Zhang, and Ms Yayun Fang from Zhongnan Hospital of Wuhan University. This study was supported in part by grants from the Fundamental Research Funds for the Central Universities (2042018kf1040), the Chinese Central Special Fund for Local Science and Technology Development of Hubei Province (2018ZYYD023), the Science and Technology Department of Hubei Province Key Project (2018ACA159), and the Wuhan Science and Technology Bureau Key Project (2018061005132294). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the paper.

Author information

Author notes

  1. These authors contributed equally: Yejinpeng Wang, Lingao Ju

Authors and Affiliations

  1. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China

    Yejinpeng Wang, Yu Xiao & Xinghuan Wang

  2. Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China

    Lingao Ju, Kaiyu Qian & Yu Xiao

  3. Human Genetic Resources Preservation Center of Hubei Province, Wuhan, China

    Lingao Ju, Kaiyu Qian & Yu Xiao

  4. Department of Urology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China

    Zicheng Guo & Hongbo Chen

  5. Euler Technology, Beijing, China

    Yi Zhang

Authors
  1. Yejinpeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lingao Ju
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zicheng Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaiyu Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hongbo Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yu Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xinghuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.W. and X.W. designed and performed the research, analyzed the data, and prepared the figures. Y.W., L.J., Z.G., K.Q., and Y.Z. performed and analyzed the research. L.J., Y.X., and X.W. supervised the study. Z.G., K.Q., and H.C. provided patient samples. Y.W. wrote the paper, and L.J. and Y.X. edited the paper. All authors approved the final version of the paper.

Corresponding authors

Correspondence to Yu Xiao or Xinghuan Wang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics

Clinical, pathological, and follow-up data records for all BCa patients and their family members were collected (Table S1), and two pathologists were invited to independently confirm the histological diagnosis. Additional cancer patient samples were collected through clinical practice at the Zhongnan Hospital of Wuhan University. The study used human samples (urine, tissue section, and plasma) and was approved by the Institutional Ethics Review Committee (approval number: 2015029). Human sample preservation by the Zhongnan Hospital Biobank, the official member of the International Society for Biological and Environmental Repositories (https://irlocator.isber.org/details/60), was approved by the Ethics Committee (approval number: 2017038) and China Human Genetic Resources Management Office, Ministry of Science and Technology of China (approval number: 20171793). All BCa patients and family members provided written informed consent. All study procedures were performed in accordance with the ethical standards of the Institutional Ethics Review Committee.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Ju, L., Guo, Z. et al. Pedigree analysis of a POLD1 germline mutation in urothelial carcinoma shows a close association between different mutation burdens and overall survival. Cell Mol Immunol 18, 767–769 (2021). https://doi.org/10.1038/s41423-020-0425-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41423-020-0425-8

This article is cited by

Search

Advanced search

Quick links