Abstract
BackgroundThe CBFA2T3 locus located on the human chromosome region 16q24.3 is frequently deleted in breast tumors. CBFA2T3 gene expression levels are aberrant in breast tumor cell lines and the CBFA2T3B isoform is a potential tumor suppressor gene. In the absence of identified mutations to further support a role for this gene in tumorigenesis, we explored whether the CBFA2T3B promoter region is aberrantly methylated and whether this correlates with expression.ResultsAberrant hypo and hypermethylation of the CBFA2T3B promoter was detected in breast tumor cell lines and primary breast tumor samples relative to methylation index interquartile ranges in normal breast counterpart and normal whole blood samples. A statistically significant inverse correlation between aberrant CBFA2T3B promoter methylation and gene expression was established.ConclusionCBFA2T3B is a potential breast tumor suppressor gene affected by aberrant promoter methylation and gene expression. The methylation levels were quantitated using a second-round real-time methylation-specific PCR assay. The detection of both hypo and hypermethylation is a technicality regarding the methylation methodology.
Highlights
The CBFA2T3 locus located on the human chromosome region 16q24.3 is frequently deleted in breast tumors
The methylation status of a high-density CpG island promoter region located five prime to the exon 1B sequence of the CBFA2T3B transcript is described (Figure 1A). We explored whether this region is aberrantly methylated in breast tumor cell lines and primary breast tumor samples and whether a correlation exists between methylation and gene expression
The tumor suppressor activity previously shown for CBFA2T3B, led us to examine the expression profile of this transcript in breast tumor cell lines using a TaqMan probe specific for exon 1B
Summary
The CBFA2T3 locus located on the human chromosome region 16q24.3 is frequently deleted in breast tumors. CBFA2T3 gene expression levels are aberrant in breast tumor cell lines and the CBFA2T3B isoform is a potential tumor suppressor gene. Sequencing of the 3-Mb region has identified approximately 100 genes [4] Eight of these have been excluded as potential tumor suppressors for breast cancer based on mutation analysis in tumor DNA [5]. A messenger RNA (mRNA) expression survey was completed within 2.4-Mb of this region examining the expression profiles of over 75 genes in a panel of breast tumor cell lines [6]. It was found that only three genes exhibited significantly aberrant expression profiles. These genes were highly expressed in some cell lines and lowly expressed in others. This led to the hypothesis that this (page number not for citation purposes)
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