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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2014

01-12-2014 | Translational Research and Biomarkers

Allelic Imbalance at an 8q24 Oncogenic SNP is Involved in Activating MYC in Human Colorectal Cancer

Authors: Keishi Sugimachi, MD, PhD, Atsushi Niida, PhD, Ken Yamamoto, MD, PhD, Teppei Shimamura, PhD, Seiya Imoto, PhD, Hisae Iinuma, PhD, Yoshiaki Shinden, MD, Hidetoshi Eguchi, MD, PhD, Tomoya Sudo, MD, PhD, Masahiko Watanabe, MD, PhD, Junichi Tanaka, MD, PhD, Shinei Kudo, MD, PhD, Kazuo Hase, MD, PhD, Masato Kusunoki, MD, PhD, Kazutaka Yamada, MD, PhD, Yasuhiro Shimada, MD, PhD, Kenichi Sugihara, MD, PhD, Yoshihiko Maehara, MD, PhD, Satoru Miyano, PhD, Masaki Mori, MD, PhD, Koshi Mimori, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 4/2014

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Abstract

Background

The rs6983267 at 8q24.21 has been established as a significant cancer-related single nucleotide polymorphism (SNP). The risk allele showed similarity to the binding site of transcription factor TCF4/LEF1 that activates transcription of MYC. However, little is known about the role of this SNP in increasing MYC activity in colorectal cancers (CRCs).

Methods

The genotypes of rs6983267 in peripheral blood and primary cancers, MYC activity and copy number (CN) alteration were examined in 107 CRCs. Next, we plotted the number of cancers cell lines exhibiting specific G/T genotypes in 746 cancer cell lines of the Sanger Institute database. Then we validated the relationship between the 8q24 SNP status and clinicopathologic parameters in 68 CRCs with loss of heterozygosity (LOH).

Results

The MYC module activity was activated by either transcription in the risk allele (G) or by amplification in the non-risk allele (T). Then, we confirmed that the CN amplification dominantly occurred in the non-risk allele, whereas CN neutral LOH, which indicated uniparental disomy (UPD) was more frequently observed for the risk allele. Finally, we confirmed that risk allele dominant cases, either by amplification or by UPD, indicated a more malignant clinical phenotype than non-risk allele dominant cases.

Conclusions

The development of CRC requires MYC activation through retention of the risk allele, or amplification of the non-risk allele at the oncogenic SNP in the site of primary tumor.
Appendix
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Metadata
Title
Allelic Imbalance at an 8q24 Oncogenic SNP is Involved in Activating MYC in Human Colorectal Cancer
Authors
Keishi Sugimachi, MD, PhD
Atsushi Niida, PhD
Ken Yamamoto, MD, PhD
Teppei Shimamura, PhD
Seiya Imoto, PhD
Hisae Iinuma, PhD
Yoshiaki Shinden, MD
Hidetoshi Eguchi, MD, PhD
Tomoya Sudo, MD, PhD
Masahiko Watanabe, MD, PhD
Junichi Tanaka, MD, PhD
Shinei Kudo, MD, PhD
Kazuo Hase, MD, PhD
Masato Kusunoki, MD, PhD
Kazutaka Yamada, MD, PhD
Yasuhiro Shimada, MD, PhD
Kenichi Sugihara, MD, PhD
Yoshihiko Maehara, MD, PhD
Satoru Miyano, PhD
Masaki Mori, MD, PhD
Koshi Mimori, MD, PhD
Publication date
01-12-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 4/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3468-6

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