The simian virus SV40 (SV40), a potent DNA oncogenic polyomavirus, has been detected in several human tumors including lymphomas, mainly in diffuse large B-cell type (DLBCL). However, a causative role for this virus has not been convincingly established. Hypermethylation in promoter regions is a frequent process of silencing tumor suppressor genes (TSGs) in cancers, which may be induced by oncogenic viruses. In this study, we investigated the relationship between the presence of SV40 DNA sequences and the methylation status of 13 TSGs in 108 DLBCLs and 60 nontumoral samples from Tunisia. SV40 DNA presence was investigated by PCR assays targeting the large T-antigen, the regulatory and the VP1 regions. Hypermethylation was carried out by methylationspecific PCR. SV40 DNA was detected in 63/108 (56%) of DLBCL and in 4/60 (6%) of nontumoral samples. Hypermethylation frequencies for the tested TSGs were 74% for DAPK, 70% for CDH1, SHP1, and GSTP1, 58% for p16, 54% for APC, 50% for p14, 39% for p15, 19% for RB1, 15% for BLU, 3% for p53, and 0% for p300 and MGMT. No hypermethylation was observed in nontumoral samples. Hypermethylation of SHP1, DAPK, CDH1, GSTP1 and p16 genes were significantly higher in SV40-positive than in SV40-negative DLBCL samples (p values ranging from 0.0006 to <0.0001). Our findings showed a high prevalence of SV40 DNA in DLBCLs in Tunisia. The significant association of promoter hypermethylation of multiple TSGs with the presence of SV40 DNA in DLBCLs supports a functional effect of the virus in those lymphomas. ' 2007 Wiley-Liss, Inc.Key words: diffuse large B-cell lymphomas; simian virus 40; hypermethylation; tumor suppressor genes; Tunisia Simian virus 40 (SV40) is a potent DNA oncogenic polyomavirus of rhesus monkey origin which seems to have spread to human beings via contamination of poliovirus stocks between 1955 and 1963 as well as by other means, 1 and mounting evidence suggests that it is an emergent human pathogen. 2-4 SV40 DNA sequences have been detected in pediatric and adult brain tumors, 5,6 mesotheliomas, 7 osteosarcomas, 8 bronchopulmonary carcinomas, 9 bone tumors 10 and papillary thyroid carcinomas. 11 There also increasing evidence that SV40 is associated with non-Hodgkin's lymphomas, particularly with diffuse large B-cell lymphomas (DLBCL), 12-21 in spite of several negative studies. [22][23][24] However, although these observations indicate an association between this virus and specific human tumors, they do not demonstrate a causal role, and the molecular mechanism by which SV40 thought to be involved is still unclear.SV40 oncogenic potential is assumed to be associated with the primary viral gene product, large T-antigen (Tag), protein responsible for SV40 replication and SV40-mediated cell transformation. 1 In vitro, the infection of human cells by SV40 has showed that SV40 Tag can promote malignancy transformation by blocking the products of several tumor suppressor genes (TSGs), 1,25 inducing telomerase activity, 26 and stimulating other oncogenes and growth facto...
HighlightsIntestinal intussusception in adults is rare, accounting for approximately 1% of all bowel obstructions.Colo-colonic intussusception accounts for 17% of cases.The occurrence of large lipomatous masses as cause of intussusception and semi-obstructive symptoms remains rare.The case that we describe is particularly unique because apart from being an example of intussusception in adults, it occurred in the sigmoid colon and was not associated with a malignant lesion.
The objective was to determine the demographic characteristics, the clinical features, the immuno-histological findings and response to treatment of childhood linear IgA bullous dermatosis (LABD) in Tunisia. We collected all the cases of auto-immune bullous diseases of childhood, diagnosed from January 1987 to December 2006. Based on clinical, histological, and immunofluorescent features, we identified 25 cases of LABD. Sixteen male and nine female children with a mean age of 7.5 years were identified. Clinical manifestations were characterized by a vesiculo-bullous eruption in all cases associated with mucous membrane involvement in two cases. Dapsone was the main therapy in 19 cases, associated with systemic corticosteroids in eight cases. Exclusive antibiotic therapy was successful in five cases. Sixteen of those patients had resolution of disease after a mean period of 15 months and eight patients had severe clinical presentation and required a prolonged follow-up. Childhood LABD is the most frequent bullous dermatosis in Tunisia. The majority of our patients responded rapidly to dapsone treatment and were stabilized for long time. Our cases were characterized by a minimal mucosal involvement and favorable outcome. Treatment with antibiotherapy was interesting. Erythromycin and oxacillin may be considered as an alternative therapy.
Cole disease is a genodermatosis of pigmentation following a strict dominant mode of inheritance. In this study, we investigated eight patients affected with an overlapping genodermatosis after recessive inheritance. The patients presented with hypo- and hyperpigmented macules over the body, resembling dyschromatosis universalis hereditaria in addition to punctuate palmoplantar keratosis. By homozygosity mapping and whole-exome sequencing, a biallelic p.Cys120Arg mutation in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was identified in all patients. We found that this mutation, like those causing dominant Cole disease, impairs homodimerization of the ENPP1 enzyme that is mediated by its two somatomedin-B-like domains. Histological analysis revealed structural and molecular changes in affected skin that were likely to originate from defective melanocytes because keratinocytes do not express ENPP1. Consistently, RNA-sequencing analysis of patient-derived primary melanocytes revealed alterations in melanocyte development and in pigmentation signaling pathways. We therefore conclude that germline ENPP1 cysteine-specific mutations, primarily affecting the melanocyte lineage, cause a clinical spectrum of dyschromatosis, in which the p.Cys120Arg allele represents a recessive and more severe form of Cole disease.
We conclude that the prevalence of EBV-associated GC in Tunisia is low (4.1%), suggesting that this virus is not an important etiological factor in GC arising in north African populations. The clinicopathological profile of EBV-associated GC in Tunisia did not differ markedly from that found elsewhere.
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