title: The rs6983267 SNP is associated with MYC transcription efficiency, which promotes progression and worsens prognosis of colorectal cancer.
abstract: BACKGROUND
  The oncogenic single nucleotide polymorphism rs6983267, located on 8q24.21, may affect copy number aberrations and/or expression profiles in colorectal cancer (CRC). We investigated the role of this single nucleotide polymorphism in the clinical outcome of CRC.
  
  
  METHODS
  Array comparative genomic hybridization (aCGH) and oligomicroarrays were performed on cancer cells from 157 primary CRC tissues. Expression profiles were analyzed by means of extraction expression module (EEM) analyses. Mutations in TP53, KRAS, and BRAF and microsatellite instability were also examined in 107 of the 157 cases.
  
  
  RESULTS
  aCGH analysis revealed two clusters; more frequent genomic copy number alteration (CNA) was observed in the 89 cases in cluster B than in the 18 cases in cluster A. The average CNA was higher in samples containing the major allele (GT/TT) of rs6983267 than in those containing the minor allele (GG). Additionally, MYC expression was the highest in samples containing the GG allele (n = 18), followed by the GT and TT alleles (n = 41 and 48, respectively). EEM analysis revealed dominant up-regulation of MYC in samples containing the minor allele. Moreover, the presence of the minor allele in a MYC-positive, CNA-negative context predicted a poorer prognosis than the presence of the major allele in a MYC-negative, CNA-positive context in CRC.
  
  
  CONCLUSIONS
  The presence of the minor allele of rs6983267 at 8q24.21 worsened the prognosis of CRC through up-regulation of MYC transcription. Furthermore, progression of CRC may require global CNA in the presence of the major allele and with lack of MYC transcription.
authors.affiliation: Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takatsuno
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sato
authors.forename: Atsushi
authors.initials: A
authors.lastname: Niida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Seiya
authors.initials: S
authors.lastname: Imoto
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kawano
authors.forename: Rui
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Toh
authors.forename: Hisae
authors.initials: H
authors.lastname: Iinuma
authors.forename: Shinya
authors.initials: S
authors.lastname: Ishimaru
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.forename: Shinkan
authors.initials: S
authors.lastname: Tokudome
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Tanaka
authors.forename: Shin-Ei
authors.initials: SE
authors.lastname: Kudo
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yamada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Moriya
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger