Hypermethylation Analysis of p16INK4a and p15INK4b Promoters in Chronic Lymphocytic Leukaemia Patients and Normal Individuals
- Author:
Amira M
- Collective Name: Sarina S, Rosline H , Azlan H , Muhammad Farid J , Chang KM
- Publication Type:Journal Article
- Keywords:
Chronic Lymphocytic Leukaemia, Methylation-specific PCR, DNA sequencing, p16INK4a , p15INK4b
- From:
The International Medical Journal Malaysia
2019;18(1):35-44
- CountryMalaysia
- Language:English
-
Abstract:
Introduction: Chronic Lymphocytic Leukaemia (CLL) is a common type of leukaemia in persons of
predominantly European descent but is rare in the Asian population. Disparities in CLL incidence among
people of Asian and European descent may be related to the genetic make-up of the two different
populations. Hypermethylation event might be one of the silencing mechanisms that inactivate the tumour
suppressor genes in CLL. The aim of this study was to determine the hypermethylation status of p16INK4a and
p15INK4b among CLL patients and normal individuals. Materials & Methods: A total of 25 CLL patients and 25
normal individuals were recruited for this study and their genomic DNA were extracted from the peripheral
blood. The hypermethylation status of p16INK4a and p15INK4b were determined using Methylation Specific-PCR
(MS-PCR) whereas DNA sequencing method was applied to selected samples for validation of the MS-PCR
results. We also evaluated the association between hypermethylation of these genes with the clinical and
demographic characteristics of each group of subjects. Results: Among the CLL patients, p15INK4b partialmethylation occurred in 6 (24%) subjects while methylation occurred in 1 (4%) subject. All the remaining
patients were unmethylated at p15INK4b. All the samples showed unmethylation at p16INK4a. Statistically
significant associations were found between p15INK4b hypermethylation with the presence of CLL (p=0.01) and
with race (p=0.02). Conclusion: Further study using a larger sample size is warranted to explore the
significance of DNA methylation incidence among the CLL patients of the Malaysian population. Hence, we
suggest that hypermethylation at p15INK4b has a huge influence that kick-starts CLL disease among Malaysians
and MS-PCR technique is applicable to be used in methylation study.
- Full text:180107.pdf
