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Ben Dhiab M.,Farhat Hached Hospital of Sousse | Ziadi S.,Farhat Hached Hospital of Sousse | Ksiaa F.,Farhat Hached Hospital of Sousse | Louhichi T.,Farhat Hached Hospital of Sousse | And 5 more authors.
Tumor Biology | Year: 2015

Deregulation of the microRNA miR124a by DNA methylation has been implicated in various malignancies, but no study reported its methylation status in Hodgkin lymphoma (HL). We evaluated the methylation of the three loci encoding for miR124a using methylation-specific PCR in 64 HL patients and 15 reactive lymph nodes obtained from patients with nonmalignant diseases. Results were correlated with clinicopathological parameters. Methylation rates of miR124a-1, miR124a-2, and miR124a-3 in HL were 17, 50, and 28 %, respectively. None of the nontumoral samples showed aberrant hypermethylation in any of the miR tested. In HL cases, we found that miR124a-1 methylation correlates with high-risk International Prognostic Score (IPS) (score >3, p = 0.04) and that miR124a-2 methylation was more frequent in children (82.3 %, p = 0.006) and men (63.9 %, p = 0.01). Methylation of miR124a-3 was associated with advanced Ann-Arbor stages (p = 0.007). The survival analysis showed that methylation of at least one of the miR124a genes was associated with shortened event-free survival in univariate (p = 0.03) and multivariate (p = 0.02) analyses. These results suggest that miR124a methylation is associated with aggressive HL disease and may be an interesting factor for predicting treatment response. © 2014, International Society of Oncology and BioMarkers (ISOBM).


PubMed | Farhat Hached Hospital of Sousse
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2015

Deregulation of the microRNA miR124a by DNA methylation has been implicated in various malignancies, but no study reported its methylation status in Hodgkin lymphoma (HL). We evaluated the methylation of the three loci encoding for miR124a using methylation-specific PCR in 64 HL patients and 15 reactive lymph nodes obtained from patients with nonmalignant diseases. Results were correlated with clinicopathological parameters. Methylation rates of miR124a-1, miR124a-2, and miR124a-3 in HL were 17, 50, and 28%, respectively. None of the nontumoral samples showed aberrant hypermethylation in any of the miR tested. In HL cases, we found that miR124a-1 methylation correlates with high-risk International Prognostic Score (IPS) (score >3, p=0.04) and that miR124a-2 methylation was more frequent in children (82.3%, p=0.006) and men (63.9%, p=0.01). Methylation of miR124a-3 was associated with advanced Ann-Arbor stages (p=0.007). The survival analysis showed that methylation of at least one of the miR124a genes was associated with shortened event-free survival in univariate (p=0.03) and multivariate (p=0.02) analyses. These results suggest that miR124a methylation is associated with aggressive HL disease and may be an interesting factor for predicting treatment response.


PubMed | Farhat Hached Hospital of Sousse
Type: Journal Article | Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | Year: 2010

JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P=0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years (P=0.034) and in the intestinal histological type (P=0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P=0.007 and P=0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases (P=0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan-Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P=0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.

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