Aberrant CBFA2T3B gene promoter methylation in breast tumors.
BACKGROUND
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. 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.


RESULTS
Aberrant 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.


CONCLUSIONS
CBFA2T3B 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.
Bais
Anthony J
AJ
Bionomics Limited, Thebarton, Adelaide, SA 5031, Australia. abais@bionomics.com.au
Gardner
Alison E
AE
McKenzie
Olivia L D
OL
Callen
David F
DF
Sutherland
Grant R
GR
Kremmidiotis
Gabriel
G
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008745:Methylation; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017422:Sequence Analysis, DNA / Q000379:methods; D013447:Sulfites / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
C115744:CBFA2T3 protein, human; D004273:DNA, Neoplasm; D010750:Phosphoproteins; D021122:Protein Subunits; D012097:Repressor Proteins; D013447:Sulfites; D025521:Tumor Suppressor Proteins; C042345:hydrogen sulfite