Methylation Analysis of Several Tumour Suppressor Genes Shows a Low Frequency of Methylation ofCDKN2AandRARBin Uveal Melanomas

We have investigated the frequency of methylation of several tumour suppressor genes in uveal melanoma. As the loss of one copy of chromosome 3 (monosomy 3), which is found in about half of these tumours, is tightly associated with metastatic disease, a special emphasis was laid on genes located on this chromosome, including the fragile histidine triad (FHIT), von Hippel–Lindau (VHL), β-catenin (CTNNB1), activated leukocyte cell adhesion molecule (ALCAM) and retinoic acid receptor-β2 (RARB) genes. In addition, the methylation patterns of the CpG-rich regions 5′ of the E-cadherin (CDH1), p16/cyclin-dependent kinase inhibitor 2 A (CDKN2A) and retinoblastoma (RB1) genes were analysed by bisulphite genomic sequencing or methylation-specific PCR (MSP). Furthermore, the SNRPN andD15S63loci, which are located in the imprinted region of chromosome 15, were included in the study. Aberrant methylation was detected in nine of 40 tumours analysed: The imprintedSNRPNandD15S63loci were hypermethylated in three tumours, all of which retained both copies of chromosome 3. MethylatedRARBalleles were detected in three tumours, whereas in three other tumoursCDKN2Awas found to be methylated. As we did not find RARB and CDKN2A preferentially methylated in tumours with monosomy 3, which is a significant predictor of metastatic disease, we suggest that these genes may play a causative role in the formation of uveal melanoma but not in the development of metastases.

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ACCELERATED PAPER: Identification of human tumour suppressor genes by monochromosome transfer: rapid growth-arrest response mapped to 9p21 is mediated solely by the cyclin-D-dependent kinase inhibitor gene, CDKN2A(p16INK4A)

Carcinogenesis ◽

10.1093/carcin/17.8.1567 ◽

1996 ◽

Vol 17 (8) ◽

pp. 1567-1575 ◽

Cited By ~ 25

Author(s):

Nicole L. England ◽

Andrew P. Cuthbert ◽

Deborah A. Trott ◽

Sarah Jezzard ◽

Tsutomu Nobori ◽

...

Keyword(s):

Rapid Growth ◽

Kinase Inhibitor ◽

Growth Arrest ◽

Tumour Suppressor ◽

Tumour Suppressor Genes ◽

Cyclin D ◽

Human Tumour ◽

Suppressor Genes ◽

Inhibitor Gene

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Aberrant methylation of tumour suppressor genes WT1, GATA5 and PAX5 in hepatocellular carcinoma

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2015-1198 ◽

2016 ◽

Vol 54 (12) ◽

Cited By ~ 8

Author(s):

Martin Mžik ◽

Marcela Chmelařová ◽

Stanislav John ◽

Jan Laco ◽

Ondřej Slabý ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Promoter Methylation ◽

Mrna Level ◽

Methylation Status ◽

Tumour Suppressor ◽

Tumour Suppressor Genes ◽

Aberrant Methylation ◽

Suppressor Genes ◽

Tissue Samples ◽

Differentially Methylated Genes

AbstractBackground:Aberrant hypermethylation of tumour suppressor genes (TSGs) occurring in hepatocellular carcinoma (HCC) could provide a mean of molecular characterisation of this cancer. The aim of this study was to investigate promoter methylation and gene expression of selected TSGs in HCC to identify candidate genes for further validation as potential biomarkers.Methods:Methylation-specific multiplex ligation-dependent probe amplification method was used to measure the methylation status of 25 TSGs in 49 HCC samples and 36 corresponding non-cancerous liver tissue samples. Relative expression of the differentially methylated genes was assessed at the mRNA level using quantitative PCR.Results:We observed a significantly higher methylation in genesConclusions:HCC evince aberrant promoter methylation of

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Aberrant Methylation Status of Tumour Suppressor Genes in Ovarian Cancer Tissue and Paired Plasma Samples

International Journal of Molecular Sciences ◽

10.3390/ijms20174119 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4119 ◽

Cited By ~ 2

Author(s):

Dana Dvorská ◽

Dušan Braný ◽

Bálint Nagy ◽

Marián Grendár ◽

Robert Poka ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumour Suppressor ◽

Tumour Suppressor Genes ◽

Aberrant Methylation ◽

Potential Candidate ◽

Plasma Samples ◽

Cdh1 Gene ◽

Suppressor Genes ◽

Non Invasive ◽

Malignant Lesions

Ovarian cancer is a highly heterogeneous disease and its formation is affected by many epidemiological factors. It has typical lack of early signs and symptoms, and almost 70% of ovarian cancers are diagnosed in advanced stages. Robust, early and non-invasive ovarian cancer diagnosis will certainly be beneficial. Herein we analysed the regulatory sequence methylation profiles of the RASSF1, PTEN, CDH1 and PAX1 tumour suppressor genes by pyrosequencing in healthy, benign and malignant ovarian tissues, and corresponding plasma samples. We recorded statistically significant higher methylation levels (p < 0.05) in the CDH1 and PAX1 genes in malignant tissues than in controls (39.06 ± 18.78 versus 24.22 ± 6.93; 13.55 ± 10.65 versus 5.73 ± 2.19). Higher values in the CDH1 gene were also found in plasma samples (22.25 ± 14.13 versus 46.42 ± 20.91). A similar methylation pattern with positive correlation between plasma and benign lesions was noted in the CDH1 gene (r = 0.886, p = 0.019) and malignant lesions in the PAX1 gene (r = 0.771, p < 0.001). The random forest algorithm combining methylation indices of all four genes and age determined 0.932 AUC (area under the receiver operating characteristic (ROC) curve) prediction power in the model classifying malignant lesions and controls. Our study results indicate the effects of methylation changes in ovarian cancer development and suggest that the CDH1 gene is a potential candidate for non-invasive diagnosis of ovarian cancer.

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