Aberrant Methylation of Tumour Suppressor Gene ADAM12 in Chronic Lympocytic Leukemia Patients: Application of Methylation Specific-PCR Technique

18540 Background: Transcriptional silencing represents a major mechanism of tumour suppressor gene inactivation in human tumours, including lymphoma. Here, we have compared patterns of aberrant methylation in sporadic and HIV-associated B cell lymphomas. Methods: We used methylation reversal/ micro-array analysis to seek novel genes subject to methylation-dependent transcriptional silencing in B cell lymphoma cell lines and primary B cell lymphomas from immune competent and HIV positive patients. Results: We describe the identification from these studies of a number of genes previously unreported as human tumour suppressors that are subject to transcriptional silencing in B lymphomas. Analysis of a subset of these genes, together with a panel of previously identified transcriptionally-silenced genes in primary B lymphomas, both sporadic and HIV-associated, revealed that patterns of aberrant methylation were highly conserved between the two patient groups. In contrast, we found no epigenetic changes in any of the analysed genes in EBV-immortalised B lymphoblastoid cell lines. Conclusions: These studies show that a similar subset of genes is subject to methylation-dependent transcriptional silencing in B lymphomas in sporadic and HIV-associated cases, implying that the same tumour suppressor pathways are inactivated and arguing that, at least epigenetically, these disorders are very similar disease entities. No significant financial relationships to disclose.

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TP53 and C-MYC Co-Alterations – A Hallmark of Oral Cancer Progression / SIMULTANA ALTERACIJA TP53 I C-MYC GENA – OBELEŽJE PROGRESIJE ORALNIH KARCINOMA

Journal of Medical Biochemistry ◽

10.2478/jomb-2014-0009 ◽

2013 ◽

Vol 32 (4) ◽

pp. 380-388 ◽

Cited By ~ 1

Author(s):

Nasta Tanić ◽

Jelena Milašin ◽

Tatjana Dramićanin ◽

Maja Bošković ◽

Miroslav Vukadinović ◽

...

Keyword(s):

Oral Cancer ◽

Cancer Progression ◽

Squamous Cell ◽

Suppressor Gene ◽

Tumour Suppressor Gene ◽

Tumour Suppressor ◽

Pcr Analysis ◽

Squamous Cell Carci ◽

Myc Oncogene ◽

Specific Pcr

Summary Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. There- fore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to esti- mate amplification status of c-myc, cycD1 and EGFR onco- genes, mutational PCR-SSCP analysis to determine activa- tion of H-ras oncogene and inactivation of TP55 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycD1 in 20% and EGFR in 16.7% of Oral Squamous Cell Carci- noma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associat- ed with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycD1 and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP55 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC pro- gression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP55 and c-myc, it seems that co- alteration of these two genes could be also a good marker of OSCC progression from gradel to grade 2 tumours.

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