The rs6983267 SNP Is Associated with MYC Transcription Efficiency, Which Promotes Progression and Worsens Prognosis of Colorectal Cancer

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• 作者：Yasushi Takatsuno MD (1) (13)
  Koshi Mimori MD ; PhD (1)
  Ken Yamamoto PhD (2)
  Tetsuya Sato PhD (4)
  Atsushi Niida PhD (3)
  Hiroshi Inoue MD ; PhD (1)
  Seiya Imoto PhD (3)
  Shuhei Kawano PhD (3)
  Rui Yamaguchi PhD (3)
  Hiroyuki Toh PhD (4)
  Hisae Iinuma MD ; PhD (5)
  Shinya Ishimaru MD ; PhD (1) (13)
  Hideshi Ishii MD ; PhD (1) (14)
  Sadao Suzuki MD ; PhD (6)
  Shinkan Tokudome MD ; PhD (6)
  Masahiko Watanabe MD ; PhD (7)
  Jun-ichi Tanaka MD ; PhD (8)
  Shin-ei Kudo MD ; PhD (8)
  Hidetaka Mochizuki MD ; PhD (9)
  Masato Kusunoki MD ; PhD (10)
  Kazutaka Yamada MD ; PhD (11)
  Yasuhiro Shimada MD ; PhD (12)
  Yoshihiro Moriya MD ; PhD (12)
  Satoru Miyano PhD (3)
  Kenichi Sugihara MD ; PhD (13)
  Masaki Mori MD ; PhD ; FACS (14)
  
• 刊名：Annals of Surgical Oncology
• 出版年：2013
• 出版时间：April 2013
• 年：2013
• 卷：20
• 期：4
• 页码：1395-1402
• 全文大小：789KB
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• 作者单位：Yasushi Takatsuno MD (1) (13)
  Koshi Mimori MD, PhD (1)
  Ken Yamamoto PhD (2)
  Tetsuya Sato PhD (4)
  Atsushi Niida PhD (3)
  Hiroshi Inoue MD, PhD (1)
  Seiya Imoto PhD (3)
  Shuhei Kawano PhD (3)
  Rui Yamaguchi PhD (3)
  Hiroyuki Toh PhD (4)
  Hisae Iinuma MD, PhD (5)
  Shinya Ishimaru MD, PhD (1) (13)
  Hideshi Ishii MD, PhD (1) (14)
  Sadao Suzuki MD, PhD (6)
  Shinkan Tokudome MD, PhD (6)
  Masahiko Watanabe MD, PhD (7)
  Jun-ichi Tanaka MD, PhD (8)
  Shin-ei Kudo MD, PhD (8)
  Hidetaka Mochizuki MD, PhD (9)
  Masato Kusunoki MD, PhD (10)
  Kazutaka Yamada MD, PhD (11)
  Yasuhiro Shimada MD, PhD (12)
  Yoshihiro Moriya MD, PhD (12)
  Satoru Miyano PhD (3)
  Kenichi Sugihara MD, PhD (13)
  Masaki Mori MD, PhD, FACS (14)
  
  1. Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan
  13. Department of Surgical Oncology, Tokyo Medical and Dental University, Tokyo, Japan
  2. Department of Molecular and Cellular Biology, Kyushu University, Fukuoka, Japan
  4. Division of Molecular Design, Kyushu University, Fukuoka, Japan
  3. Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
  5. Department of Surgery, Teikyo University, Tokyo, Japan
  14. Department of Gastroenterological Surgery, Osaka University, Suita, Japan
  6. Department of the Public Health, Nagoya City University, Nagoya, Japan
  7. Department of Surgery, Kitazato University, Kanagawa, Japan
  8. Digestive Disease Center, Northern Yokohama Hospital, Showa University, Yokohama, Japan
  9. Department of Surgery, Defence Medical College, Tokorozawa, Japan
  10. Department of Surgery, Mie University, Mie, Japan
  11. Department of Surgery, Takano Hospital, Kumamoto, Japan
  12. Department of Surgery and Digestive Tract Medicine, National Cancer Center, Tokyo, Japan
  

文摘

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.