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. 2021 Aug;21(5):938-941.
doi: 10.1016/j.pan.2021.03.015. Epub 2021 Mar 28.

Examination of ATM, BRCA1, and BRCA2 promoter methylation in patients with pancreatic cancer

Affiliations

Examination of ATM, BRCA1, and BRCA2 promoter methylation in patients with pancreatic cancer

Cancan Zhou et al. Pancreatology. 2021 Aug.

Abstract

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.

Keywords: Cancer; CpG island; Inherited; Methylation; Pancreas.

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Conflict of interest statement

Declaration of competing interest R.H.H has the right to receive royalty payments from Thrive Earlier Diagnosis for the GNAS in pancreatic cysts invention. The authors declare no other conflicts of interest.

Figures

Figure 1.
Figure 1.. Methylation of ATM, BRCA1 and BRCA2 promoter CpG islands in patients with pancreatic cancer.
Percent methylation of ATM, BRCA1 and BRCA2 promoter CpG islands for 655 patients with pancreatic cancer. No patient had promoter methylation greater than 3.4%, 3.3%, and 7.6% respectively, indicating that no patient had inherited variants that promote constitutive methylation of these regions.

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