Ziguo Yang1, Tao Ouyang1, Jinfeng Li1, Tianfeng Wang1, Zhaoqing Fan1, Tie Fan1, Benyao Lin1, Juan Zhang2, Yuntao Xie3. 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. 2. 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. zhangjuan100@126.com. 3. 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. zlxyt2@bjmu.edu.cn.
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.
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 cancerpatients. METHODS: A multi-gene panel was performed to screen for ATM germline mutations in 7657 BRCA1/2-negative breast cancerpatients. 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.
Entities:
Keywords:
ATM gene; Breast cancer; Chinese population; Germline mutation
Authors: Xiaoran Liu; Andrew A Davis; Feng Xie; Xinyu Gui; Yifei Chen; Qiang Zhang; Lorenzo Gerratana; Youbin Zhang; Ami N Shah; Amir Behdad; Firas Wehbe; Yong Huang; Jianjun Yu; Pan Du; Shidong Jia; Huiping Li; Massimo Cristofanilli Journal: Breast Cancer Res Treat Date: 2021-09-01 Impact factor: 4.872
Authors: Marcella Nunziato; Federica Di Maggio; Matilde Pensabene; Maria Valeria Esposito; Flavio Starnone; Carmine De Angelis; Alessandra Calabrese; Massimiliano D'Aiuto; Gerardo Botti; Sabino De Placido; Valeria D'Argenio; Francesco Salvatore Journal: Front Med (Lausanne) Date: 2022-08-11