抑癌基因 ADAM12 在慢性淋巴细胞白血病患者中的异常甲基化：甲基化特异性 PCR 技术的应用。
Aberrant Methylation of Tumour Suppressor Gene ADAM12 in Chronic Lympocytic Leukemia Patients: Application of Methylation Specific-PCR Technique.
机构信息
Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
出版信息
Asian Pac J Cancer Prev. 2021 Jan 1;22(1):85-91. doi: 10.31557/APJCP.2021.22.1.85.
OBJECTIVE
Chronic Lymphocytic Leukemia (CLL) is a common leukemia among Caucasians but rare in Asians population. We postulated that aberrant methylation either hypermethylation or partial methylation might be one of the silencing mechanisms that inactivates the tumour suppressor genes in CLL. This study aimed to compare the methylation status of tumour suppressor gene, ADAM12, among CLL patients and normal individuals. We also evaluated the association between methylation of ADAM12 and clinical and demographic characteristics of the participants.
METHODS
A total of 25 CLL patients and 25 normal individuals were recruited in this study. The methylation status of ADAM12 was determined using Methylation-Specific PCR (MSP); whereas, DNA sequencing method was applied for validation of the MSP results.
RESULTS
Among CLL patients, 12 (48%) were partially methylated and 13 (52%) were unmethylated. Meanwhile, 5 (20%) and 20 (80.6%) of healthy individuals were partially methylated and unmethylated, respectively. There was a statistically significant association between the status of methylation at ADAM12 and the presence of CLL (p=0.037).
CONCLUSION
The aberrant methylation of ADAM12 found in this study using MSP assay may provide new exposure to CLL that may improve the gaps involved in genetic epigenetic study in CLL.
目的
慢性淋巴细胞白血病（CLL）在白种人群中较为常见，但在亚洲人群中较为罕见。我们推测，异常甲基化（包括过度甲基化或部分甲基化）可能是沉默 CLL 中肿瘤抑制基因的机制之一。本研究旨在比较 CLL 患者和正常个体中肿瘤抑制基因 ADAM12 的甲基化状态。我们还评估了 ADAM12 甲基化与参与者临床和人口统计学特征之间的关联。
方法
本研究共纳入 25 例 CLL 患者和 25 例正常个体。采用甲基化特异性 PCR（MSP）检测 ADAM12 的甲基化状态；同时，应用 DNA 测序法验证 MSP 结果。
结果
在 CLL 患者中，有 12 例（48%）呈部分甲基化，13 例（52%）呈非甲基化。而在健康个体中，有 5 例（20%）和 20 例（80.6%）分别呈部分甲基化和非甲基化。ADAM12 甲基化状态与 CLL 的存在之间存在统计学显著关联（p=0.037）。
结论
本研究采用 MSP 检测到 ADAM12 的异常甲基化，可能为 CLL 提供新的认识，有助于填补 CLL 中遗传表观遗传学研究的空白。
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