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

  • Preclinical study
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

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Abbreviations

ATM :

The ataxia telangiectasia-mutated gene

ANOVA:

One-way analysis of variance

DSB:

DNA double-strand break

ER:

Oestrogen receptor

FAT:

FRAP-ATM-TRRAP

HER2:

Human epidermal growth factor receptor 2

IHC:

Immunohistochemical

PARP:

Poly (ADP-ribose) polymerase

PCR:

Polymerase chain reaction

PIK:

PI-3 kinase

PR:

Progesterone receptor

SD:

Standard deviation

TNBC:

Triple-negative breast cancer

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Acknowledgements

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

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Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, 100142, Beijing, People’s Republic of China

    Ziguo Yang, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Juan Zhang & Yuntao Xie

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  1. Ziguo Yang
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  2. Tao Ouyang
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  3. Jinfeng Li
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  4. Tianfeng Wang
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  8. Juan Zhang
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Correspondence to Juan Zhang or Yuntao Xie.

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

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Written informed consent was obtained from all participants.

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Yang, Z., Ouyang, T., Li, J. et al. Prevalence and characterization of ATM germline mutations in Chinese BRCA1/2-negative breast cancer patients. Breast Cancer Res Treat 174, 639–647 (2019). https://doi.org/10.1007/s10549-018-05124-5

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