Breast Cancer Research and Treatment

, Volume 169, Issue 1, pp 59–67 | Cite as

Identification and analysis of CHEK2 germline mutations in Chinese BRCA1/2-negative breast cancer patients

  • Zhenhua Fan
  • Tao Ouyang
  • Jinfeng Li
  • Tianfeng Wang
  • Zhaoqing Fan
  • Tie Fan
  • Benyao Lin
  • Ye Xu
  • Yuntao Xie
Preclinical study



Cell-cycle-checkpoint kinase 2 (CHEK2) is an important moderate-penetrance breast cancer predisposition gene; however, recurrent CHEK2 mutations found in Caucasian women are very rare in Chinese population. We investigated the mutation spectrum and clinical relevance of CHEK2 germline mutations in Chinese breast cancer patients.


The entire coding regions and splicing sites of CHEK2 were screened in 7657 Chinese BRCA1/2-negative breast cancer patients, using 62-gene panel-based sequencing.


Out of 7657 BRCA1/2-negative breast cancer patients, 26 (0.34%) carried CHEK2 pathogenic germline mutations. Most of these mutations (92.3%, 24/26) were nonsense or frameshift mutations; 84.6% (22/26) of them were in forkhead-associated (FHA) or kinase domains. Of the 18 types of CHEK2 mutations we found, 61.1% (11/18) of were novel mutations and two recurrent mutations (Y139X and R137X) were found in this cohort. Patients with CHEK2 mutations were significantly more likely to have family histories of breast and/or ovarian cancer (23.1% vs. 8.6%, p = 0.022) and family histories of any cancer (50.0% vs. 31.6%, p = 0.044); and were significantly more likely to have lymph node-positive (53.8% vs. 27.3%, p = 0.002) and progesterone receptor (PR)-positive (88.5% vs. 64.5%, p = 0.011) breast cancers.


Among Chinese breast cancer patients, the CHEK2 germline mutation rate is approximately 0.34% and two specific mutations (Y139X and R137X) are recurrent. Patients with CHEK2 mutations are significantly more likely to have family histories of cancer, and to develop lymph node-positive and/or PR-positive breast cancers.


CHEK2 Germline mutation Breast cancer Chinese population 



This study was supported by the National Natural Science Foundation of China (81372832 and 81202107), the National Science and Technology Support Program (2014BAI09B08), and the 973 project (2013CB911004).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Supplementary material

10549_2018_4673_MOESM1_ESM.pdf (342 kb)
Supplementary material 1 (PDF 342 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Breast Center, Peking University Cancer Hospital & InstituteBeijingPeople’s Republic of China

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