Deletion hotspots in AMACR promoter CpG island are cis-regulatory elements controlling the gene expression in the colon.

PLoS Genetics
Xiang ZhangShuk-Mei Ho

Abstract

Alpha-methylacyl-coenzyme A racemase (AMACR) regulates peroxisomal beta-oxidation of phytol-derived, branched-chain fatty acids from red meat and dairy products -- suspected risk factors for colon carcinoma (CCa). AMACR was first found overexpressed in prostate cancer but not in benign glands and is now an established diagnostic marker for prostate cancer. Aberrant expression of AMACR was recently reported in Cca; however, little is known about how this gene is abnormally activated in cancer. By using a panel of immunostained-laser-capture-microdissected clinical samples comprising the entire colon adenoma-carcinoma sequence, we show that deregulation of AMACR during colon carcinogenesis involves two nonrandom events, resulting in the mutually exclusive existence of double-deletion at CG3 and CG10 and deletion of CG12-16 in a newly identified CpG island within the core promoter of AMACR. The double-deletion at CG3 and CG10 was found to be a somatic lesion. It existed in histologically normal colonic glands and tubular adenomas with low AMACR expression and was absent in villous adenomas and all CCas expressing variable levels of AMACR. In contrast, deletion of CG12-16 was shown to be a constitutional allele with a frequency of ...Continue Reading

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Citations

Nov 6, 2013·Annual Review of Medicine·C Thomas CaskeyAmy L McGuire
May 17, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ying-En LeeChien-Feng Li
Sep 2, 2010·PloS One·Regina Berretta, Pablo Moscato
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Aug 8, 2020·Frontiers in Molecular Biosciences·Gyeyeong KongJongsun Park
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Nov 12, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chien-Feng LiHsuan-Ying Huang

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Datasets Mentioned

BETA
EF636492
EF636496

Methods Mentioned

BETA
PCR
ChIP
PCRs
ChIP-chip
immunoprecipitation
transfection
Assay
X-ray
deamination

Software Mentioned

ClustalW
SAS Proc Genmod
BLAST
MatInspector

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