Prevalence and characterization of ATM germline mutations in Chinese BRCA1/2-negative breast cancer patients

  • Ziguo Yang
  • Tao Ouyang
  • Jinfeng Li
  • Tianfeng Wang
  • Zhaoqing Fan
  • Tie Fan
  • Benyao Lin
  • Juan ZhangEmail author
  • Yuntao XieEmail author
Preclinical study



The ataxia telangiectasia-mutated (ATM) gene is a moderate susceptibility gene for breast cancer. However, little is known about the breast cancer phenotypes associated with ATM mutation. We therefore investigated the spectrum and clinical characteristics of ATM germline mutations in Chinese breast cancer patients.


A multi-gene panel was performed to screen for ATM germline mutations in 7657 BRCA1/2-negative breast cancer patients. All deleterious mutations were validated by independent polymerase chain reaction (PCR)-Sanger sequencing.


A total of 31 pathogenic mutations in the ATM gene across 30 carriers were identified, and the ATM mutation rate was 0.4% (30/7,657) in this cohort. The majority of the mutations (90.3%, 28/31) were nonsense or frameshift mutations. Of the total ATM mutations, 61.3% (19/31) were novel mutations and 13 recurrent mutations were found. ATM mutations carriers were significantly more likely to have a family history of breast and/or ovarian cancer (26.7% in carriers vs. 8.6% in non-carriers, p < 0.001), as well as a family history of any cancer (60.0% in carriers vs. 31.5% in non-carriers, p = 0.001). In addition, ATM mutations carriers were significantly more likely to have oestrogen receptor (ER)-positive (p = 0.011), progesterone receptor (PR)-positive (p = 0.040), and lymph node-positive breast cancer (p = 0.034).


The prevalence of the ATM mutation is approximately 0.4% in Chinese BRCA1/2-negative breast cancer. ATM mutation carriers are significantly more likely to have a family history of cancer and to develop ER- and/or PR-positive breast cancer or lymph node-positive breast cancer.


ATM gene Germline mutation Breast cancer Chinese population 



The ataxia telangiectasia-mutated gene


One-way analysis of variance


DNA double-strand break


Oestrogen receptor




Human epidermal growth factor receptor 2




Poly (ADP-ribose) polymerase


Polymerase chain reaction


PI-3 kinase


Progesterone receptor


Standard deviation


Triple-negative breast cancer



This study was supported by the National Natural Science Foundation of China (81772824, 81773209 and 81372832).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was conducted in accordance with Helsinki Declaration, and was approved by the Research Ethics Committee of Peking University Cancer Hospital.

Informed consent

Written informed consent was obtained from all participants.

Supplementary material

10549_2018_5124_MOESM1_ESM.doc (70 kb)
Supplementary material 1 (DOC 70 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

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

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