Publications

Shedding New Light on ATM loss and Role in Pancreatic Cancer Risk

Pancreatic cancer is caused by the accumulation of multiple genetic changes that can either be inherited or acquired during a person’s lifetime. Inheriting a disease-causing variant in the ATM gene is associated with an increased risk of developing pancreatic cancer. However, as there are two copies of the ATM gene in every cell, a second genetic change must be acquired in ATM during a person’s lifetime to result in the development of pancreatic cancer. In this study, we used DNA sequencing and immunostaining of benign precursor lesions and regions of cancer from patients with an inherited disease-causing ATM variant to determine when ATM is lost during the development of pancreatic cancer. We found that loss of ATM is almost exclusively restricted to regions of cancer and not benign precursor lesions. Furthermore, we found that ATM loss is more frequent in a subtype of pancreatic cancers called colloid carcinomas. These findings indicate that loss of ATM is a late event in the development of pancreatic cancer and may predispose to colloid carcinomas. This information may be important for the development of clinical surveillance initiatives and intervention strategies for patients with inherited disease-causing ATM variants.