Aberrant methylation of the Adenomatous Polyposis Coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype.
Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter occurs in about 40% of breast tumours and has been correlated with reduced APC protein levels. To what extent epigenetic alterations of the APC gene may differ according to specific breast cancer phenotypes, remains to be elucidated. Our aim was to explore the role of APC methylation in the inflammatory breast cancer (IBC) phenotype. The status of APC gene promoter hypermethylation was investigated in DNA from normal breast tissues, IBC and non-IBC by both conventional and real-time quantitative methylation-specific PCR (MSP). APC methylation levels were compared with APC mRNA and protein levels. Hypermethylation of the APC gene promoter was present in 71% of IBC samples (n=21) and 43% of non-IBC samples (n=30) by conventional MSP (P=0.047). The APC gene also showed an increased frequency of high methylation levels in IBC (in 74% of cases, n=19) vs non-IBC (in 46% of cases, n=35) using a qMSP assay (P=0.048). We observed no significant association between APC methylation levels by qMSP and APC mRNA or protein expression levels. In conclusion, for the first time, we report the association of aberrant methylation of the APC gene promoter with the IBC phenotype, which might be of biological and clinical importance.
Translational Cancer Research Group Antwerp, Lab Pathology University of Antwerp/University Hospital Antwerp, Edegem, Belgium.
I
I
Van der Auwera
S J
SJ
Van Laere
S M
SM
Van den Bosch
G G
GG
Van den Eynden
B X
BX
Trinh
P A
PA
van Dam
C G
CG
Colpaert
M
M
van Engeland
E A
EA
Van Marck
P B
PB
Vermeulen
L Y
LY
Dirix
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast; D001943:Breast Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D017491:Genes, APC; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D011401:Promoter Regions, Genetic; D055815:Young Adult