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:

Response to the correspondence referring to our article “Development of an MSI-positive colon tumor with aberrant DNA methylation in a PPAP patient” by Pilar Mur, Claire Palles, Ian Tomlinson, Laura Valle

Journal of Human Genetics volume 65, pages 515–516 (2020)Cite this article

Subjects

I am grateful for giving us the opportunity to comment on the correspondence by Mur et al. referring to our article “Development of an MSI-positive colon tumor with aberrant DNA methylation in a PPAP patient”.

As Mur and colleagues pointed out our data of genetic alteration, c.4191_4192delCT (p.Tyr1398*) in POLE, alone may not be enough to prove that the alteration is responsible for PPAP. However, we do not have convincing data to conclude that the variant is benign or that it does not affect the susceptibility to colorectal cancer. The variant should thus be categorized as a variant of uncertain significance (VUS). Segregation analysis would certainly be helpful for the evaluation of its pathogenicity, but unfortunately, we were unable to obtain samples from the relatives.

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. Easton DF, Lesueur F, Decker B, Michailidou K, Li J, Allen J, et al. No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing. J Med Genet. 2016;53:298–309.

    Article  CAS  Google Scholar 

  2. Weber-Lassalle N, Hauke J, Ramser J, Richters L, Groß E, Blümcke B, et al. BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer. Breast Cancer Res. 2018;20:7.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan

    Kiyoshi Yamaguchi & Yoichi Furukawa

Authors
  1. Kiyoshi Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoichi Furukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoichi Furukawa.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

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

Yamaguchi, K., Furukawa, Y. Response to the correspondence referring to our article “Development of an MSI-positive colon tumor with aberrant DNA methylation in a PPAP patient” by Pilar Mur, Claire Palles, Ian Tomlinson, Laura Valle. J Hum Genet 65, 515–516 (2020). https://doi.org/10.1038/s10038-020-0752-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s10038-020-0752-8

Search

Advanced search

Quick links