Oncotarget

Research Papers:

Targeted exome sequencing of Korean triple-negative breast cancer reveals homozygous deletions associated with poor prognosis of adjuvant chemotherapy-treated patients

Hae Min Jeong, Ryong Nam Kim, Mi Jeong Kwon, Ensel Oh, Jinil Han, Se Kyung Lee, Jong-Sun Choi, Sara Park, Seok Jin Nam, Gyung Yup Gong, Jin Wu Nam, Doo Ho Choi, Hannah Lee, Byung-Ho Nam, Yoon-La Choi and Young Kee Shin _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:61538-61550. https://doi.org/10.18632/oncotarget.18618

Metrics: PDF 725 views  |   HTML 1887 views  |   ?  


Abstract

Hae Min Jeong1, Ryong Nam Kim1,2, Mi Jeong Kwon3,4, Ensel Oh5,6, Jinil Han7, Se Kyung Lee8, Jong-Sun Choi9, Sara Park9, Seok Jin Nam8, Gyung Yup Gong10, Jin Wu Nam11, Doo Ho Choi12, Hannah Lee13, Byung-Ho Nam14, Yoon-La Choi5,6,15 and Young Kee Shin1,2,16,17

1Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, South Korea

2Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, South Korea

3College of Pharmacy, Kyungpook National University, Daegu, South Korea

4Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu, South Korea

5Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, South Korea

6Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

7Gencurix Inc., Seoul, South Korea

8Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

9The Center for Anti-Cancer Companion Diagnostics, Bio-MAX/N-Bio, Seoul National University, Seoul, South Korea

10Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

11Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, South Korea

12Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

13Interdisciplinary Program in Bioinformatics, College of Natural Science, Seoul National University, Seoul, South Korea

14HERINGS, The Institute of Advanced Clinical & Biomedical Research, Seoul, South Korea

15Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea

16The Center for Anti-Cancer Companion Diagnostics, School of Biological Science, Institutes of Entrepreneurial BioConvergence, Seoul National University, Seoul, South Korea

17Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea

Correspondence to:

Young Kee Shin, email: ykeeshin@snu.ac.kr

Yoon-La Choi, email: ylachoi@skku.edu

Keywords: triple-negative breast cancer, targeted exome sequencing, single nucleotide variant, copy number variation, DNA repair pathway

Received: December 30, 2016     Accepted: May 31, 2017     Published: June 27, 2017

ABSTRACT

Triple-negative breast cancer is characterized by the absence of estrogen and progesterone receptors and human epidermal growth factor receptor 2, and is associated with a poorer outcome than other subtypes of breast cancer. Moreover, there are no accurate prognostic genes or effective therapeutic targets, thereby necessitating continued intensive investigation. This study analyzed the genetic mutation landscape in 70 patients with triple-negative breast cancer by targeted exome sequencing of tumor and matched normal samples. Sequencing showed that more than 50% of these patients had deleterious mutations and homozygous deletions of DNA repair genes, such as ATM, BRCA1, BRCA2, WRN, and CHEK2. These findings suggested that a large number of patients with triple-negative breast cancer have impaired DNA repair function and that therefore a poly ADP-ribose polymerase inhibitor may be an effective drug in the treatment of this disease. Notably, homozygous deletion of three genes, EPHA5, MITF, and ACSL3, was significantly associated with an increased risk of recurrence or distant metastasis in adjuvant chemotherapy-treated patients.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 18618