检测胰腺癌患者 ATM、BRCA1 和 BRCA2 启动子甲基化。
Examination of ATM, BRCA1, and BRCA2 promoter methylation in patients with pancreatic cancer.
机构信息
Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
Pancreatology. 2021 Aug;21(5):938-941. doi: 10.1016/j.pan.2021.03.015. Epub 2021 Mar 28.
BACKGROUND
Pancreatic cancer is a lethal disease with a poor 5-year survival rate. Pathogenic germline variants in the coding regions of ATM, BRCA1, and BRCA2 are found in up to 4.8% of pancreatic cancer patients. Germline promoter methylation and gene silencing arising from a germline variant or through other mechanisms have been described as a cause of tumor suppressor gene inactivation.
METHODS
We measured the level of promoter methylation of the ATM, BRCA1, and BRCA2 genes in peripheral blood lymphocytes from 655 patients with pancreatic cancer using real-time PCR.
RESULTS
No evidence of germline promoter methylation of any of these genes was found. Promoter methylation levels were minimal with no patient having promoter methylation greater than 3.4%, 3.3%, and 7.6% for ATM, BRCA1 and BRCA2, respectively, well below levels found in patients who have inherited promoter methylation (∼50%).
CONCLUSIONS
We found no evidence of germline promoter methylation for the pancreatic susceptibility genes ATM, BRCA1 and BRCA2 in patients with pancreatic cancer. This study reveals that constitutive germline methylation of promoter CpG islands is rare in pancreatic cancer.
背景
胰腺癌是一种致命疾病，5 年生存率很低。多达 4.8%的胰腺癌患者存在 ATM、BRCA1 和 BRCA2 编码区的致病性种系变异。种系变异或通过其他机制引起的启动子甲基化和基因沉默被认为是肿瘤抑制基因失活的原因。
方法
我们使用实时 PCR 测量了 655 例胰腺癌患者外周血淋巴细胞中 ATM、BRCA1 和 BRCA2 基因的启动子甲基化水平。
结果
未发现这些基因的种系启动子甲基化证据。启动子甲基化水平很低，没有患者的启动子甲基化水平大于 ATM、BRCA1 和 BRCA2 的 3.4%、3.3%和 7.6%，远低于遗传性启动子甲基化患者的水平（约 50%）。
结论
我们在胰腺癌患者中未发现 ATM、BRCA1 和 BRCA2 易感性基因的种系启动子甲基化证据。本研究表明，胰腺癌中组成型种系 CpG 岛甲基化很少见。
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