title: Frequent CpG methylation of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in sporadic and hereditary Tunisian breast cancer patients: clinical significance.
abstract: Aberrant methylation of the CpG islands in promoter regions is one of the mechanisms for inactivation of tumor suppressor genes in many human cancers including breast carcinoma. In this study, we aimed to assess, by methylation-specific PCR, the CpG methylation pattern of the UCHL1 promoter in 94 sporadic and 44 hereditary breast cancers from Tunisian patients. The percentage of UCHL1 methylation was 67 % in sporadic and 82 % in hereditary breast cancer cases. In sporadic cases, UCHL1 methylation correlated with poor response to treatment (P = 0.042) and progesterone receptor status (P = 0.036), whereas in patients with hereditary predisposition, the only significant association was found with Her2 expression (P = 0.024). Moreover, in patients with sporadic breast cancer, the UCHL1 unmethylated pattern conferred a prolonged overall survival time in particular in the group of patients with advanced TNM stage of the disease (P log rank = 0.04). Aberrant CpG methylation of the UCHL1 promoter was significantly associated with transcriptional silencing of this tumor suppressor gene in sporadic breast cancer tissues (P = 0.001). On the other hand, the UCHL1 unmethylated pattern correlated with P53 positivity in primary sporadic tumors (P = 0.032), supporting the functional link between the two tumor suppressors in breast tumorigenesis.
authors: Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins, Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour street, BP"K"1177, 3018 Sfax, Tunisia.
authors: Fatma
authors: F
authors: Trifa
authors: Sondes
authors: S
authors: Karray-Chouayekh
authors: Zeineb Ben
authors: ZB
authors: Jmaa
authors: Emna
authors: E
authors: Jmal
authors: Abdelmajid
authors: A
authors: Khabir
authors: Tahia
authors: T
authors: Sellami-Boudawara
authors: Mounir
authors: M
authors: Frikha
authors: Jamel
authors: J
authors: Daoud
authors: Raja
authors: R
authors: Mokdad-Gargouri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014416:Tunisia; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase