title: CpG methylation of APC promoter 1A in sporadic and familial breast cancer patients.
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.
authors.affiliation: Laboratory of Molecular Biotechnology of Eukaryotes, Department of Cancer Genetics, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
authors.forename: Saoussen
authors.initials: S
authors.lastname: Debouki-Joudi
authors.affiliation: Laboratory of Molecular Biotechnology of Eukaryotes, Department of Cancer Genetics, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
authors.forename: Fatma
authors.initials: F
authors.lastname: Trifa
authors.affiliation: Centre Hospitalo-Universitaire Habib Bourguiba, Sfax 3000, Tunisia.
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Khabir
authors.affiliation: Centre Hospitalo-Universitaire Habib Bourguiba, Sfax 3000, Tunisia.
authors.forename: Tahia
authors.initials: T
authors.lastname: Sellami-Boudawara
authors.affiliation: Centre Hospitalo-Universitaire Habib Bourguiba, Sfax 3000, Tunisia.
authors.forename: Mounir
authors.initials: M
authors.lastname: Frikha
authors.affiliation: Centre Hospitalo-Universitaire Habib Bourguiba, Sfax 3000, Tunisia.
authors.forename: Jamel
authors.initials: J
authors.lastname: Daoud
authors.affiliation: Laboratory of Molecular Biotechnology of Eukaryotes, Department of Cancer Genetics, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
authors.forename: Raja
authors.initials: R
authors.lastname: Mokdad-Gargouri
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D014416:Tunisia
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein
keywords: APC; Breast cancer; CpG methylation; epigenetic; transcriptional silencing