Affiliations: [a] Laboratory of Molecular Biotechnology of Eukaryotes, Department of Cancer Genetics, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia | [b] Centre Hospitalo-Universitaire Habib Bourguiba, Sfax 3000, Tunisia
Correspondence:
[*]
Corresponding author: Raja Mokdad-Gargouri, Laboratory of Molecular Biotechnology of Eukaryotes, Department of Cancer Genetics, Center of Biotechnology of Sfax, Sidi Mansour Street, BP``K''1177-Sfax, 3018, University of Sfax, Sfax, Tunisia. Tel./Fax: +216 74 874 449; E-mail:[email protected]
Abstract: Tumour suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer
initiation. The aim of this study was to assess the extent of methylation of APC gene promoter in 91 sporadic and 44
familial cases of Tunisian patients with breast cancer (BC) in. The frequency of APC promoter methylation is somewhat
similar for sporadic and familial breast cancer cases, (52.1%, and 54.5% respectively). For sporadic breast cancer patients,
there was a significant correlation of APC promoter hypermethylation with TNM stage (p = 0.024) and 3-year survival (p = 0.025). Regarding the hormonal status (HR), we found significant association between negativity to PR and unmethylated APC
(p= 0.005) while ER and Her2/neu are not correlated. Moreover, unmethylated APC promoter is more frequent in tumours expressing at least one out the 3 proteins compared to triple negative cases (p= 0.053). On the other hand,
aberrant methylation of APC was associated with tumour size (p = 0.036),
lymph node (p = 0.028), distant metastasis (p = 0.031), and
3-year survival (p = 0.046) in the group of patients with familial breast
cancer. Moreover, patients with sporadic breast cancer displaying the
unmethylated profile have a significant prolonged overall survival compared
to those with the methylated pattern of APC promoter (p log rank = 0.008). Epigenetic
change at the CpG islands in the APC promoter was associated with the
silence of its transcript and the loss of protein expression suggesting that
this event is the main mechanism regulating the APC expression in breast
cancer. In conclusion, our data showed that the loss of APC through aberrant
methylation is associated with the aggressive behavior of both sporadic and
familial breast cancer in Tunisian patients.
Keywords: Breast cancer, APC, CpG methylation, transcriptional silencing, epigenetic
