Research Papers:
Targeted exome sequencing of Korean triple-negative breast cancer reveals homozygous deletions associated with poor prognosis of adjuvant chemotherapy-treated patients
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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: [email protected]
Yoon-La Choi, email: [email protected]
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.
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