KRAS mutation analysis by droplet digital PCR of duodenal juice from patients with MODY8 and other pancreatic diseases

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Vol. 21; no. 8; pp. 1460 - 1465
• Main Authors: Choi, Man Hung, Tjora, Erling, Forthun, Rakel Brendsdal, Engjom, Trond, Ræder, Helge, Hovland, Randi, Molven, Anders
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01.12.2021; Elsevier Limited
• Subjects: Abundance; Acute Disease; Adenocarcinoma; Age; Cancer; Carcinoma, Pancreatic Ductal; Chronic pancreatitis; Codons; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2; Disease; Droplet digital PCR; Duodenal juice; Gastrointestinal diseases; Gene frequency; Humans; Juices; K-Ras protein; KRAS; Middle Aged; MODY8; Mutation; Mutation analysis; Pancreatic cancer; Pancreatic diseases; Pancreatic Juice; Pancreatic Neoplasms; Pancreatic Neoplasms - genetics; Pancreatitis; Patients; Polymerase Chain Reaction; Proteins; Proto-Oncogene Proteins p21(ras) - genetics; Statistical analysis; Norway; MODY8; Chronic pancreatitis; Pancreatic cancer; Duodenal juice; Droplet digital PCR; KRAS; Mutation analysis
• ISSN: 1424-3903; 1424-3911; 1424-3911
• DOI: 10.1016/j.pan.2021.09.010

Maturity-onset diabetes of the young type 8 (MODY8 or CEL-MODY) is an inherited pancreatic disease characterized by chronic inflammation of the pancreas and diabetes. It is not known whether MODY8 patients have increased risk for developing pancreatic cancer. We investigated KRAS mutation load in duodenal juice from MODY8 patients, comparing with other groups of pancreatic disease. Droplet digital PCR (ddPCR) was used to detect KRAS codon 12/13/61 mutations in duodenal juice sampled from 11 MODY8 patients, nine healthy subjects and 100 patients clinically investigated due to suspected pancreatic disease. KRAS mutations were detected in 4/11 patients with MODY8 (36%), 1/9 healthy subjects (11%), 15/44 patients with chronic pancreatitis (CP, 34%), 3/5 patients with pancreatic ductal adenocarcinoma (PDAC, 60%), 3/20 patients with acute pancreatitis (15%), 0/13 patients with other pancreatic disorders and 2/18 patients with nonpancreatic gastrointestinal disease (11%). Of the 28 positive juice samples, 25 (89%) had low-abundance mutations in codons 12/13, with a variant allele frequency (VAF) less than 1%. KRAS-positive patients with MODY8 or CP had significantly lower VAFs than patients with PDAC (Mann-Whitney U test; p = 0.041). Although the overall mutation detection rate was higher for subjects ≥50 years old (26%) than for younger subjects (15%), the difference was not statistically significant. KRAS mutations were detectable in duodenal juice from MODY8 patients, but with low abundance and at the same frequency as in CP patients. The discriminative value of the analysis with regard to other pancreatic disease was limited.