Amanda Lussier, MD, Sooraj Srirangadhamu Gopu, MD, Omar Alkasabrah, MD, Jatin Thukral, MD, Garron Lamp, MD Landmark Medical Center, Woonsocket, RI Introduction: Exocrine pancreatic cancer is considered the fourth leading cause of cancer-related deaths in the United States. Ductal adenocarcinomas account for approximately 85% of pancreatic neoplasms. The CHEK2 mutation is associated with an increased risk of breast, stomach, and prostate cancers; however, it is rarely observed in patients with pancreatic cancer. This report highlights a case of pancreatic adenocarcinoma with a CHEK2 mutation.
Case Description/
Methods: A 45-year-old male with history of hypertension presented to the hospital with 2 weeks of jaundice, diarrhea, and decreased appetite. He expressed episodic abdominal discomfort 6 months ago with associated 45 lb weight loss; CT abdomen/pelvis was negative at that time. Lab workup on admission revealed elevated GGT 1352, AST 256, ALT 204, total bilirubin 11.4, direct bilirubin 8.6. Hepatitis screening was negative. CT and MRCP revealed a 3.2 cm pancreatic head mass encasing the SMA with multiple liver lesions up to 3.3 cm, and intra- and extrahepatic bile duct dilation. Staging PET scan that confirmed a hypermetabolic pancreatic head mass, peripancreatic lymph nodes, and liver metastasis. EUS and FNA of peripancreatic node was positive for stage 4 pancreatic adenocarcinoma. Patient underwent ERCP with sphincterotomy, biliary stenting, and brushing for liver decompression with findings of ampullary stenosis, and intrapancreatic CBD strictures. He was started on FOLFIRINOX chemotherapy. NGS testing revealed TP53, KRAS with tumor mutation burden of 8.6, but no actionable targets or high MSI. Germline testing revealed a p.l157T (C.470T >C) moderate risk mutation in CHEK 2 gene. Discussion: The CHEK 2 protein maintains genomic stability by controlling the cell cycle, repairing damaged DNA, and participating in apoptosis. One major pathogenic CHEK 2 mutation identified is I175T. The I175T mutation is a missense mutation where Isoleucine at position 157 is changed to Threonine. This genetic variant poses an increased risk for multi-organ cancers such as breast cancer, colon cancer, kidney cancer, prostate cancer, and thyroid cancer [1]. Few studies have shown CHEK 2 I175T mutation contributing to Familial Pancreatic Cancer and minimal involvement in sporadic cases. Our case highlights CHEK 2 I175T mutation in metastatic pancreatic cancer in a patient without risk factors or family history. The CHEK 2 I175T mutation is associated with low penetrance of disease and studies linking this variant to hereditary pancreatic cancer remain limited.
Disclosures: Amanda Lussier indicated no relevant financial relationships. Sooraj Srirangadhamu Gopu indicated no relevant financial relationships. Omar Alkasabrah indicated no relevant financial relationships. Jatin Thukral indicated no relevant financial relationships. Garron Lamp indicated no relevant financial relationships.
Amanda Lussier, MD, Sooraj Srirangadhamu Gopu, MD, Omar Alkasabrah, MD, Jatin Thukral, MD, Garron Lamp, MD. P0184 - Genomic Stability Interrupted: A Case of CHEK2 I157T Mutation in Metastatic Pancreatic Adenocarcinoma, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
