title: Rapid detection of genetic mutations in individual breast cancer patients by next-generation DNA sequencing.
abstract: Breast cancer is the most common malignancy in women and the leading cause of cancer deaths in women worldwide. Breast cancers are heterogenous and exist in many different subtypes (luminal A, luminal B, triple negative, and human epidermal growth factor receptor 2 (HER2) overexpressing), and each subtype displays distinct characteristics, responses to treatment, and patient outcomes. In addition to varying immunohistochemical properties, each subtype contains a distinct gene mutation profile which has yet to be fully defined. Patient treatment is currently guided by hormone receptor status and HER2 expression, but accumulating evidence suggests that genetic mutations also influence drug responses and patient survival. Thus, identifying the unique gene mutation pattern in each breast cancer subtype will further improve personalized treatment and outcomes for breast cancer patients. In this study, we used the Ion Personal Genome Machine (PGM) and Ion Torrent AmpliSeq Cancer Panel to sequence 737 mutational hotspot regions from 45 cancer-related genes to identify genetic mutations in 80 breast cancer samples of various subtypes from Chinese patients. Analysis revealed frequent missense and combination mutations in PIK3CA and TP53, infrequent mutations in PTEN, and uncommon combination mutations in luminal-type cancers in other genes including BRAF, GNAS, IDH1, and KRAS. This study demonstrates the feasibility of using Ion Torrent sequencing technology to reliably detect gene mutations in a clinical setting in order to guide personalized drug treatments or combination therapies to ultimately target individual, breast cancer-specific mutations.
authors.affiliation: The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. liusq0909@163.com.
authors.forename: Suqin
authors.initials: S
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. wanghj2001@outlook.com.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. ailizhil@aliyun.com.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. chuanningtang@hotmail.com.
authors.forename: Chuanning
authors.initials: C
authors.lastname: Tang
authors.affiliation: Norris Comprehensive Cancer Center, Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. lindseaj@usc.edu.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Jones
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. yehua.sanvalley@gmail.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Ye
authors.affiliation: The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. bly7011@163.com.
authors.forename: Liying
authors.initials: L
authors.lastname: Ban
authors.affiliation: The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. wangaman_163@163.com.
authors.forename: Aman
authors.initials: A
authors.lastname: Wang
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. liuzhi19883304@sina.com.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. feng.lou@hotmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Lou
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. zhangdd.sanvalley@gmail.com.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. sunhong126@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. donghaichao.sanvalley@gmail.com.
authors.forename: Haichao
authors.initials: H
authors.lastname: Dong
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. zhanggc.sanvalley@gmail.com.
authors.forename: Guangchun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. dongzhishou@163.com.
authors.forename: Zhishou
authors.initials: Z
authors.lastname: Dong
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. baihychuan@hotmail.com.
authors.forename: Baishuai
authors.initials: B
authors.lastname: Guo
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. yanhe.sanvalley@gmail.com.
authors.forename: He
authors.initials: H
authors.lastname: Yan
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. ycw222009@yahoo.cn.
authors.forename: Chaowei
authors.initials: C
authors.lastname: Yan
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. 13552644544@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. suzy8802@163.com.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Su
authors.affiliation: San Valley Biotechnology Incorporated, Beijing, China. yangyangli.2007@163.com.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Norris Comprehensive Cancer Center, Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. xuefhuan@usc.edu.
authors.forename: Xue F
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Norris Comprehensive Cancer Center, Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. siyichen@usc.edu.
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. zhoutao1967@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D057285:Precision Medicine; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human