title: Aberrant methylation of hMLH1 and p16INK4a in Tunisian patients with sporadic colorectal adenocarcinoma.
abstract: The methylation of CpG islands in the promoters is associated with loss of protein via repression of gene transcription. Several studies have demonstrated that tumour suppressor and DNA repair genes are often aberrantly hypermethylated in colorectal cancer. The present study was conducted to examine whether the methylation profile of p16INK4a and hMLH1 (human mutL homologue 1) promoters was associated with clinical features and patients' survival in CRC (colorectal carcinoma). Aberrant methylation of p16INK4a and hMLH1 promoters was found in 47.2 and 53.4% of tumours respectively. For adjacent non-tumoral mucosa, p16INK4a was fully unmethylated in 30% of the cases, whereas hMLH1 was predominantly unmethylated (76%). Methylation of p16INK4a correlated with gender and tumour size (P=0.005 and 0.035 respectively), whereas those of hMLH1 significantly correlated with overall survival (P log rank=0.007). Concomitant methylation of p16INK4a and hMLH1 was associated with TNM (tumour, lymph node and metastases) stage and tumour size (P=0.024 and 0.021 respectively). Our data show that loss of hMLH1 expression through aberrant methylation could be used as a marker of poor prognosis in CRC.
authors.affiliation: Unité de Génétique du cancer et Production de protéines thérapeutiques, Centre de Biotechnologie de Sfax, Route Sidi Mansour Km 6, BP 1177, 3018 Sfax, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Miladi-Abdennadher
authors.forename: Rania
authors.initials: R
authors.lastname: Abdelmaksoud-Damak
authors.forename: Lobna
authors.initials: L
authors.lastname: Ayadi
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Khabir
authors.forename: Foued
authors.initials: F
authors.lastname: Frikha
authors.forename: Lamia
authors.initials: L
authors.lastname: Kallel
authors.forename: Mounir
authors.initials: M
authors.lastname: Frikha
authors.forename: Tahia
authors.initials: T
authors.lastname: Sellami-Boudawara
authors.forename: Ali
authors.initials: A
authors.lastname: Gargouri
authors.forename: Raja
authors.initials: R
authors.lastname: Mokdad-Gargouri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D014416:Tunisia
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019941:Cyclin-Dependent Kinase Inhibitor p16; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1