title: Allelic imbalance at an 8q24 oncogenic SNP is involved in activating MYC in human colorectal cancer.
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.
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Sugimachi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Niida
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Teppei
authors.initials: T
authors.lastname: Shimamura
authors.forename: Seiya
authors.initials: S
authors.lastname: Imoto
authors.forename: Hisae
authors.initials: H
authors.lastname: Iinuma
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shinden
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sudo
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Junichi
authors.initials: J
authors.lastname: Tanaka
authors.forename: Shinei
authors.initials: S
authors.lastname: Kudo
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hase
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: Kenichi
authors.initials: K
authors.lastname: Sugihara
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002430:Cecal Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8; D056915:DNA Copy Number Variations; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D016259:Genes, myc / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012004:Rectal Neoplasms / Q000235:genetics*; D012811:Sigmoid Neoplasms / Q000235:genetics*