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.
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Research Article|
March 02 2011
Aberrant methylation of hMLH1 and p16INK4a in Tunisian patients with sporadic colorectal adenocarcinoma
Imen Miladi-Abdennadher;
Imen Miladi-Abdennadher
*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
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Rania Abdelmaksoud-Damak;
Rania Abdelmaksoud-Damak
*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
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Lobna Ayadi;
Lobna Ayadi
†Laboratoire d’Anatomie et de cytologie Pathologiques, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, Tunisia
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Abdelmajid Khabir;
Abdelmajid Khabir
†Laboratoire d’Anatomie et de cytologie Pathologiques, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, Tunisia
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Foued Frikha;
Foued Frikha
†Laboratoire d’Anatomie et de cytologie Pathologiques, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, Tunisia
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Lamia Kallel;
Lamia Kallel
†Laboratoire d’Anatomie et de cytologie Pathologiques, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, Tunisia
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Mounir Frikha;
Mounir Frikha
†Laboratoire d’Anatomie et de cytologie Pathologiques, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, Tunisia
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Tahia Sellami-Boudawara;
Tahia Sellami-Boudawara
†Laboratoire d’Anatomie et de cytologie Pathologiques, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, Tunisia
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Ali Gargouri;
Ali Gargouri
*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
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Raja Mokdad-Gargouri
Raja Mokdad-Gargouri
1
*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
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 15 2010
Revision Received:
August 05 2010
Accepted:
September 03 2010
Accepted Manuscript online:
September 03 2010
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biosci Rep (2011) 31 (4): 257–264.
Article history
Received:
February 15 2010
Revision Received:
August 05 2010
Accepted:
September 03 2010
Accepted Manuscript online:
September 03 2010
Citation
Imen Miladi-Abdennadher, Rania Abdelmaksoud-Damak, Lobna Ayadi, Abdelmajid Khabir, Foued Frikha, Lamia Kallel, Mounir Frikha, Tahia Sellami-Boudawara, Ali Gargouri, Raja Mokdad-Gargouri; Aberrant methylation of hMLH1 and p16INK4a in Tunisian patients with sporadic colorectal adenocarcinoma. Biosci Rep 1 August 2011; 31 (4): 257–264. doi: https://doi.org/10.1042/BSR20100023
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