title: Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.
abstract: BACKGROUND
  The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS) for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs), which are abundant in solid tumors, can be utilized for identification of rearranged ends.
  
  
  METHODS
  As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB) in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP) microarray method entailing CNB-region refinement by competitor DNA.
  
  
  RESULTS
  Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9%) were identified, and two polymerase chain reaction (PCR)-amplifiable rearrangements were obtained in six cases (66.7%). And significantly, TNGS-CNB, with its high positive identification rate (82.6%) of PCR-amplifiable rearrangements at candidate sites (19/23), just from filtering of aligned sequences, requires little effort for validation.
  
  
  CONCLUSIONS
  Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.
authors.affiliation: Research Institute, National Cancer Center, Ilsandong-gu, Goyang, Korea; Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Hyun-Kyoung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Surgery, Wonkwang University School of Medicine, Iksan, Korea.
authors.forename: Won Cheol
authors.initials: WC
authors.lastname: Park
authors.affiliation: Department of Surgery, Wonkwang University School of Medicine, Iksan, Korea.
authors.forename: Kwang Man
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Research Institute, National Cancer Center, Ilsandong-gu, Goyang, Korea.
authors.forename: Hai-Li
authors.initials: HL
authors.lastname: Hwang
authors.affiliation: Research Institute, National Cancer Center, Ilsandong-gu, Goyang, Korea.
authors.forename: Seong-Yeol
authors.initials: SY
authors.lastname: Park
authors.affiliation: Research Institute, National Cancer Center, Ilsandong-gu, Goyang, Korea.
authors.forename: Sungbin
authors.initials: S
authors.lastname: Sorn
authors.affiliation: Research Institute, National Cancer Center, Ilsandong-gu, Goyang, Korea.
authors.forename: Vishal
authors.initials: V
authors.lastname: Chandra
authors.affiliation: Research Institute, National Cancer Center, Ilsandong-gu, Goyang, Korea.
authors.forename: Kwang Gi
authors.initials: KG
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Ilsandong-gu, Goyang, Korea.
authors.forename: Woong-Bae
authors.initials: WB
authors.lastname: Yoon
authors.affiliation: Laboratory of Translational Genomics, Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.affiliation: Department of Life Science, Sogang University, Seoul, Korea; Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.affiliation: Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Seoh
authors.affiliation: Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Ilsandong-gu, Goyang, Korea.
authors.forename: Kyeong-Man
authors.initials: KM
authors.lastname: Hong
mesh_terms: D056905:Chromosome Breakpoints; D003110:Colonic Neoplasms / Q000235:genetics*; D056915:DNA Copy Number Variations; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*