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01-04-2013 | Translational Research and Biomarkers

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

Authors: Yasushi Takatsuno, MD, Koshi Mimori, MD, PhD, Ken Yamamoto, PhD, Tetsuya Sato, PhD, Atsushi Niida, PhD, Hiroshi Inoue, MD, PhD, Seiya Imoto, PhD, Shuhei Kawano, PhD, Rui Yamaguchi, PhD, Hiroyuki Toh, PhD, Hisae Iinuma, MD, PhD, Shinya Ishimaru, MD, PhD, Hideshi Ishii, MD, PhD, Sadao Suzuki, MD, PhD, Shinkan Tokudome, MD, PhD, Masahiko Watanabe, MD, PhD, Jun-ichi Tanaka, MD, PhD, Shin-ei Kudo, MD, PhD, Hidetaka Mochizuki, MD, PhD, Masato Kusunoki, MD, PhD, Kazutaka Yamada, MD, PhD, Yasuhiro Shimada, MD, PhD, Yoshihiro Moriya, MD, PhD, Satoru Miyano, PhD, Kenichi Sugihara, MD, PhD, Masaki Mori, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 4/2013

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.

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Title: The rs6983267 SNP Is Associated with MYC Transcription Efficiency, Which Promotes Progression and Worsens Prognosis of Colorectal Cancer
Authors: Yasushi Takatsuno, MD
Koshi Mimori, MD, PhD
Ken Yamamoto, PhD
Tetsuya Sato, PhD
Atsushi Niida, PhD
Hiroshi Inoue, MD, PhD
Seiya Imoto, PhD
Shuhei Kawano, PhD
Rui Yamaguchi, PhD
Hiroyuki Toh, PhD
Hisae Iinuma, MD, PhD
Shinya Ishimaru, MD, PhD
Hideshi Ishii, MD, PhD
Sadao Suzuki, MD, PhD
Shinkan Tokudome, MD, PhD
Masahiko Watanabe, MD, PhD
Jun-ichi Tanaka, MD, PhD
Shin-ei Kudo, MD, PhD
Hidetaka Mochizuki, MD, PhD
Masato Kusunoki, MD, PhD
Kazutaka Yamada, MD, PhD
Yasuhiro Shimada, MD, PhD
Yoshihiro Moriya, MD, PhD
Satoru Miyano, PhD
Kenichi Sugihara, MD, PhD
Masaki Mori, MD, PhD, FACS
Publication date: 01-04-2013
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 4/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-012-2657-z

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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