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

Cancan Zhou; Nancy Porter; Michael Borges; Christian Gauthier; Lindsey Ferguson; Bo Huang; Neha Nanda; Jin He; Daniel Laheru; Ralph H Hruban; Michael Goggins; Alison P Klein; Nicholas J Roberts

doi:10.1016/j.pan.2021.03.015

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

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

Authors

Affiliations

¹ Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
⁴ Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ 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.
⁷ 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; Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: aklein1@jhmi.edu.
⁸ 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. Electronic address: nrobert8@jhmi.edu.

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.

MeSH terms

Ataxia Telangiectasia Mutated Proteins
BRCA1 Protein / genetics
BRCA2 Protein / genetics
Breast Neoplasms
DNA Methylation
Female
Genes, BRCA2
Genetic Predisposition to Disease
Humans
Pancreatic Neoplasms* / genetics
Promoter Regions, Genetic

Substances

BRCA1 Protein
BRCA1 protein, human
BRCA2 Protein
BRCA2 protein, human
ATM protein, human
Ataxia Telangiectasia Mutated Proteins

Grants and funding

P50 CA062924/CA/NCI NIH HHS/United States