Frequent epigenetic silencing of the FHIT gene in penile squamous cell carcinomas
Methylation of normally unmethylated CpG-rich islands in or near the promoter region has been associated with transcriptional inactivation of tumor-suppressor and tumor-related genes in human cancers. However, so far, only a few studies have searched for DNA methylation in penile carcinoma (PC). On the other hand, human papillomavirus (HPV) has been reported to be associated with the pathogenesis of PC. To elucidate the methylation status of PC and HPV infection, the methylation status of eight genes (DAPK, FHIT, MGMT, p14, p16, RAR-beta, RASSF1A, and RUNX3), the incidences of the HPV status, and the expression of Fhit protein were examined in 25 PCs. The frequencies of methylation were: 28% for DAPK, 92% for FHIT, 20% for MGMT, 4% for p14, 24% for p16, 24% for RAR-beta, 12% for RASSF1A, and 44% for RUNX3. Negative expression of Fhit protein was observed in 22 of the 25 cancers (88%). Among those 22, 20 showed methylation of the FHIT gene. HPV-DNA was detected in three of the 25 cancers (12%). Methylation of FHIT gene was frequently found than HPV infection, therefore methylation of the FHIT gene is suggested to play an important role in the pathogenesis of penile squamous cell carcinoma.
Available from: Maurizio D'Esposito
- "Our results are in agreement with several previous studies indicating that the loss of FHIT expression is frequent in a variety of tumors [25,26] above all in PVs induced cervical lesions [11,22,27,28]. Lowered levels of the FHIT protein were also documented in pagetoid variant of BPV induced urothelial tumour . "
[Show abstract] [Hide abstract]
ABSTRACT: Sarcoids are peculiar equine benign tumours. Their onset is associated with Bovine Papillomavirus type -1 or -2 (BPV-1/2) infection. Little is known about the molecular interplay between viral infection and neoplastic transformation. The data regarding papillomavirus infections in human species show the inactivation of a number of tumour suppressor genes as basic mechanism of transformation. In this study the putative role of the tumour suppressor gene Fragile Histidine Triad (FHIT) in sarcoid tumour was investigated in different experimental models. The expression of the oncosuppressor protein was assessed in normal and sarcoid cells and tissue.
Nine paraffin embedded sarcoids and sarcoid derived cell lines were analysed for the expression of FHIT protein by immunohistochemistry, immunofluorescence techniques and western blotting. These analyses revealed the absence of signal in seven out of nine sarcoids. The two sarcoid derived cell lines too showed a reduced signal of the protein. To investigate the causes of the altered protein expression, the samples were analysed for the DNA methylation profile of the CpG island associated with the FHIT promoter. The analysis of the 32 CpGs encompassing the region of interest showed no significative differential methylation profile between pathological tissues and cell lines and their normal counterparts.
This study represent a further evidence of the role of a tumour suppressor gene in equine sarcoids and approaches the epigenetic regulation in this well known equine neoplasm. The data obtained in sarcoid tissues and sarcoid derived cell lines suggest that also in horse, as in humans, there is a possible involvement of the tumour suppressor FHIT gene in BPV induced tumours. DNA methylation seems not to be involved in the gene expression alteration. Further studies are needed to understand the basic molecular mechanisms involved in reduced FHIT expression.
BMC Veterinary Research 03/2012; 8(1):30. DOI:10.1186/1746-6148-8-30 · 1.78 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: ObjectiveTo investigate the relationship between fragile histidine triad (FHIT) depletion and human papillomavirus (HPV) status in
the vulvar squamous cell carcinomas (VSCC).
MethodsImmunohistochemical method was used to detect the expression of FHIT protein in 42 cases of VSCC and 10 cases of normal vulvar
tissues. PCR was used to detect HPV infection status. We analyzed the relationship of the expression of FHIT protein between
the 2 groups: HPV positive and HPV negative, as well as the clinically pathological characteristics.
ResultsThe expression of FHIT was positive in all normal vulvar tissues, and 71.4% was depletion in VSCC (P < 0.01). Abnormal expression of FHIT was significantly correlated with pathological grade (P < 0.05). There was a significant diff erence between FHIT depletion and HPV infection based on the statistial analysis (P < 0.05).
ConclusionThe FHIT depletion is related to occurrence and development of VSCC, and the abnormal expression of FHIT significantly correlates
with HPV infection.
Clinical Oncology and Cancer Research 02/2009; 6(1):68-71. DOI:10.1007/s11805-009-0068-0
[Show abstract] [Hide abstract]
ABSTRACT: Epigenetics is the study of differences in phenotype, in the absence of variation in the genetic code. Epigenetics is relevant in the pathogenesis of many skin diseases. In the case of the common skin cancers, aberrant methylation of tumor suppressor gene promoters is associated with their transcriptional inactivation. Environmental carcinogens such as ultraviolet radiation and arsenic may act through epigenetic mechanisms. Hypomethylation is associated with activation of systemic autoimmune diseases, such as systemic lupus erythematosus, subacute cutaneous lupus erythematosus and scleroderma. This may be through a mechanism of immunological cross-reactivity with hypomethylated DNA from pathogenic bacteria. Epigenetic factors may also be relevant in the pathogenesis of psoriasis and other inflammatory skin diseases, as well as in the pathogenesis of the disorders of genomic imprinting with cutaneous features.
Pharmacogenomics 01/2009; 9(12):1835-50. DOI:10.2217/146224184.108.40.2065 · 3.22 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.