Effect of aberrant promoter methylation of<i>FHIT</i>and<i>RASSF1A</i>genes on susceptibility to cervical cancer in a North Indian population

Neyaz, Md. Kausar; Kumar, Rajeev; Hussain, Showket; Naqvi, Samar Husain; Kohaar, Indu; Thakur, Nisha; Kashyap, Veena; Das, Bhudev C.; Husain, Syed Akhtar; Bharadwaj, Mausumi

doi:10.1080/13547500802078859

Cited by 30 publications

(8 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results are in agreement with several previous studies indicating that the loss and or reduced expression of MGMT is frequent in a variety of tumours [25], particularly in HPV-induced cervical lesions [26-28]. It is possible that decrease of MGMT protein expression is a common mechanism of cancer development among different species.…”

Section: Discussionsupporting

confidence: 93%

O6-methylguanine-DNA methyltransferase in equine sarcoids: molecular and epigenetic analysis

et al. 2012

View full text Add to dashboard Cite

BackgroundBovine papillomaviruses (BPVs) types 1 and 2 are the only known papillomaviruses able to jump the species. In fact, BPVs 1/2 induce neoplasia in their natural bovine host but infection is also associated to neoplastic skin lesions in equids termed sarcoids. The equine sarcoid is considered to be the most common equine cutaneous tumour worldwide for which no effective therapy is available. Very little is known about the molecular mechanisms underlying tumourigenesis, although genes contributing to sarcoid development have been identified. Several studies associate the development of cancer to the loss of function of a number of oncosuppressor genes. In this study the putative role of O6-methylguanine-DNA methyltrasferase (MGMT) was investigated for sarcoids. The expression of the oncosuppressor protein was assessed in normal and sarcoid cells and tissues. In addition, the DNA methylation profile was analysed to assess the role of epigenetic mechanism in regulation of MGMT expression.ResultsA group of 15 equine sarcoids and two primary sarcoid cell lines (fibroblasts) were analyzed for the expression of MGMT protein by immunohistochemistry, immunofluorescence and Western blotting techniques. The sarcoid cell line EqSO4b and the tumour samples showed a reduction or absence of MGMT expression. To investigate the causes of deregulated MGMT expression, ten samples were analyzed for the DNA methylation profile of the CpG island associated to the MGMT promoter. The analysis of 73 CpGs encompassing the region of interest showed in 1 out of 10 (10%) sarcoids a pronouncedly altered methylation profile when compared to the control epidermal sample. Similarily the EqSO4b cell line showed an altered MGMT methylation pattern in comparison to normal fibroblasts.ConclusionAs previously demonstrated for the oncosuppressor gene FHIT, analysis of MGMT expression in sarcoid tissues and a sarcoid-derived fibroblast cell line further suggests that oncosuppressor silencing may be also involved in BPV-induced equine tumours. Abnormal DNA methylation seems to be one of the possible molecular mechanisms involved in the alteration of MGMT expression. Further studies are required to address other basic molecular mechanisms involved in reduced MGMT expression. This study underlines the possible role of DNA methylation in oncosuppressor inactivation in equine sarcoids.

show abstract

Section: Discussionsupporting

confidence: 93%

O6-methylguanine-DNA methyltransferase in equine sarcoids: molecular and epigenetic analysis

et al. 2012

View full text Add to dashboard Cite

show abstract

“…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 [18].…”

Section: Discussionsupporting

confidence: 93%

“…Several studies associate the development of cancer to the loss of function of a number of tumour suppressor genes. FHIT is a well characterized tumour suppressor gene involved in the neoplastic transformation associated to the PVs infection [11]. …”

Section: Introductionmentioning

confidence: 99%

“…It may function as intracellular and extracellular signalling molecules by interacting with specific proteins involved in the regulation of proliferative and apoptotic cellular processes [14-16]. In a variable percentage of cases, depending on the tumour type, FHIT loss of function is determined by the hypermethylation status of the associated CpG island with the consequent repression of gene transcription [11]. While alterations in the FHIT gene have been reported in several human cancers, the putative role of this tumour suppressor gene and its epigenetic alteration in animal tumours are not well known [17,18].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular and epigenetic analysis of the fragile histidine triad tumour suppressor gene in equine sarcoids

et al. 2012

View full text Add to dashboard Cite

BackgroundSarcoids 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.ResultsNine 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.ConclusionThis 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.

show abstract

“…The DNA hypomethylation and hypermethylation of several cancer-related genes have been extensively studied (8–10). In cervical cancer, DNA methylation also affects the expression of several genes, including CDH1 , DAPK , TIMP-3 , p16 (INK4a) , FHIT and RASSF1A (11,12). Unlike studies involving targeted candidate gene approaches, there have been few reports regarding genome-wide methylation profiles for investigating the methylation status of the whole genome region by using a high-density microarray-based platform.…”

Section: Introductionmentioning

confidence: 99%

Identification of differentially-expressed genes by DNA methylation in cervical cancer

et al. 2015

View full text Add to dashboard Cite

To identify novel cervical cancer-related genes that are regulated by DNA methylation, integrated analyses of genome-wide DNA methylation and RNA expression profiles were performed using the normal and tumor regions of tissues from four patients; two with cervical cancer and two with pre-invasive cancer. The present study identified 19 novel cervical cancer-related genes showing differential RNA expression by DNA methylation. A number of the identified genes were novel cervical cancer-related genes and their differential expression was confirmed in a publicly available database. Among the candidate genes, the epigenetic regulation and expression of three genes, CAMK2N1, ALDH1A3 and PPP1R3C, was validated in HeLa cells treated with a demethylating reagent using methylation-specific polymerase chain reaction (PCR) and quantitative PCR, respectively. From these results, the expression of the CAMK2N1, ALDH1A3 and PPP1R3C genes are were shown to be suppressed in cervical cancers by DNA methylation. These genes may be involved in the progression or initiation of cervical cancer.

show abstract

Effect of aberrant promoter methylation ofFHITandRASSF1Agenes on susceptibility to cervical cancer in a North Indian population

Cited by 30 publications

References 23 publications

O6-methylguanine-DNA methyltransferase in equine sarcoids: molecular and epigenetic analysis

O6-methylguanine-DNA methyltransferase in equine sarcoids: molecular and epigenetic analysis

Molecular and epigenetic analysis of the fragile histidine triad tumour suppressor gene in equine sarcoids

Identification of differentially-expressed genes by DNA methylation in cervical cancer

Contact Info

Product

Resources

About