title: Genome-wide DNA Copy-number Analysis in ACTS-CC Trial of Adjuvant Chemotherapy for Stage III Colonic Cancer.
abstract: BACKGROUND
  The adjuvant chemotherapy trial of TS-1 for colon cancer phase III trial was designed to validate the non-inferiority of the oral fluoropyrimidine S-1 to uracil and tegafur/leucovorin as adjuvant chemotherapy for stage III colonic cancer. As a prospective biomarker study of this trial, DNA copy number was studied using formalin-fixed, paraffin-embedded specimens.
  
  
  METHODS
  FFPE blocks were obtained from 795 patients of the 1,535 patients enrolled in the study. The quality of extracted DNA was assessed using arbitrarily primed polymerase chain reaction and microfluidic analysis. Genomic copy-number alterations in cancer were analyzed by high-density single-nucleotide polymorphism arrays. Copy-number changes in Japanese patients with colonic cancer were compared with those in Western countries using data from a previously reported meta-analysis. We then compared genome-wide segment copy number and clinicopathological features of colorectal cancer.
  
  
  RESULTS
  Genome-wide copy number was analyzed in 161 samples and DNA copy-number alteration profiles showed frequent DNA copy-number gains at chromosome 7, 8q and 13, and losses at 4, 5q, 8p, 17p and 18q. The weighted kappa statistic from comparing copy-number alteration status with data from Western countries was 0.828 (95% confidence interval=0.786 -0.871). DNA copy-number alterations of 8,684 segments were compared with clinicopathological features in 161 patients. Location of the tumor correlated with genomic segments of chromosome 4, 5, 7, 8, 13, 14, 18 and 20. Differentiation of the tumor correlated with segments in chromosome 4, 6, 8, 11, 13, 14,15, 16, 17 and 20.
  
  
  CONCLUSIONS
  Somatic copy-number alteration profiles of stage III colonic cancer in the Japanese ACTS-CC trial closely agreed with the results of previous Western studies. Location and differentiation of the tumor correlated with DNA copy-number alterations. Our findings will facilitate understanding the characteristics of colonic cancer. Further investigation may contribute to the exploration of valid biomarkers.
authors.affiliation: Division of Surgical Specialties, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Bunkyo-ku, Tokyo, Japan ishi.srg2@tmd.ac.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Division of Surgical Specialties, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uetake
authors.affiliation: Division of Biostatistics, Clinical Research Center, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Murotani
authors.affiliation: Translational Research Laboratory, Taiho Pharmaceutical Co., Ltd, Chiyoda-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobunai
authors.affiliation: Department of Translational Oncology, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Bunkyo-ku, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Ishiguro
authors.affiliation: Department of Biostatistics, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Matsui
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D004338:Drug Combinations; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002955:Leucovorin
keywords: ACTS-CC trial; Colonic cancer; DNA copy-number; S-1; UFT; adjuvant chemotherapy; biomarker; phase III