Analysis Of Hypermethylation Status Of Tumour Suppressor Genes P16ink4a, P15ink4b, Adam12 And Pcdhgb7 In Chronic Lymphocytic Leukaemia Patients And Normal Individuals
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Date
2017-01
Authors
Mohamad, Amira
Journal Title
Journal ISSN
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Publisher
Universiti Sains Malaysia
Abstract
Before the development of medical technology, causes of chronic lymphocytic leukaemia (CLL) remained vague and unknown. However, after the mechanisms which deactivate the function of tumour suppressor genes were discovered, the alternative mechanism that causes CLL were also discovered. The tumour suppressor genes p16INK4a, p15INK4b, ADAM12 and PCDHGB7 which might contain hypermethylation at the promoter regions are subsequently silenced in CLL patients. Hypermethylation mechanism is one of the inactivation mechanisms for tumour suppressor genes that happen in many types of cancers. We postulate amplification of hypermethylation of tumour suppressor genes p15INK4b, p16INK4a, ADAM12 and PCDHGB7 are among the silencing gene mechanisms that involve in the development and pathogenesis of CLL.
A total of 25 CLL patients and 25 normal controls were recruited as subjects in this study to obtain the peripheral blood samples. Hypermethylation amplification of tumour suppressor genes p16INK4a, p15INK4b, ADAM12 and PCDHGB7 were analysed using methylation-specific PCR (MSP) technique whereas DNA sequencing method was applied to selected samples purposely to validate the result obtained based on MSP result. We also evaluated the association between tumour suppressor genes with clinical and demographic characteristics for each subjects’ group, which are the CLL patients and normal individuals.
Among the CLL patients, hypermethylation only occurs at p15INK4b which is 2 (8%) compared to partial-methylation that occur at ADAM12 13 (52%), p15INK4b 5 (20%) and p16INK4a 1 (4%). Meanwhile, among normal controls, no hypermethylation occurs but partial-methylation occurs at ADAM12 5 (20%) and p16INK4a 2 (8%). From all of the experiments, significant associations were obtained only between hypermethylation and tumour suppressor genes p15INK4b (p = 0.01) and ADAM12 (p = 0. 037). The MSP optimisation of PCDHGB7 was unsuccessful.
Therefore, we suggested hypermethylation at p15INK4b and ADAM12 have an important role in the development of the CLL disease among Malaysian population. MSP technique is relatively cost-effective and has a high-potential to be a method of diagnosis and prognosis for CLL disease.
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Keywords
Analysis Of Hypermethylation Status , Of Tumour Suppressor Genes.